CHAPTER 1. Clinical Guideline for Adults With Diabetes

1.1.0 APPROACH TO CARE

1.1.1 Individualizing patient care:

The Joslin Clinical Guideline for Adults With Diabetes is designed to assist primary care physicians and specialists as they individualize the care of and set goals for nonpregnant adults with diabetes. This guideline focuses on the unique needs of the patient with diabetes. It is not intended to replace sound medical judgment or clinical decision making and may need to be adapted for certain patient care situations in which more or less stringent interventions may be necessary. This guideline was approved May 17, 2017, and updated May 25, 2018.

The needs and goals of each patient are unique. A treatment plan must be based on a thorough assessment and requires an understanding of not only the patient’s medical needs, but also other factors that may influence the treatment plan such as social history, race, cultural issues, ethnicity, education needs (including literacy and numeracy), comorbidities, and barriers to care. The patient’s diabetes management plan should include medical treatment, interventions, follow-up, and ongoing support. Use of the electronic medical record may help facilitate care, by enabling the team to track progress, ensuring goals are met, and facilitating communication flow among team members and the patient.

1.1.2 The patient-centered approach:

Diabetes is a condition that requires considerable selfmanagement. A collaborative counseling model that involves the patient in decisions and goal-setting helps promote behavioral change. Whenever appropriate, with the patient’s consent, involving family members and nonclinical caregivers in medical visits and education is valuable.

1.1.3 Working in a team:

Diabetes is best managed by a team, which may include clinicians, diabetes educators (DEs), dieticians, exercise physiologists, and behavioral health specialists. The patient should be informed and fully aware of what roles the various team members play. If access to a team is not possible within the office practice, it is useful to identify community resources.

Clear communication among all providers is critical to ensure patients’ needs are being met.

1.1.4 Frequency of medical visits:

While the frequency of visits for ongoing care should be individualized, monitoring the patient’s progress through medical visits is recommended at least 2 to 4 times/year. Special attention should be given to patients who do not keep scheduled appointments, have frequent hospitalizations, or miss days of work/school. Since many factors contribute to patients’ ability to manage their care, the provider should:

• Engage patients in identifying and resolving contributing factors or barriers to underutilization or overutilization of healthcare services. Patients with challenging care may benefit from consultation with endocrinologists focused on diabetes care.

• Refer to a DE, registered dietician (RD), social service professional, or behavioral health professional to address possible barriers and/or psychosocial issues

1.2.0 DIAGNOSIS OF DIABETES MELLITUS

1.2.1 General criteria for diagnosis:

• Establish a process of follow-up communication regarding adherence to the treatment plan and sustaining behaviors

The diagnosis of diabetes mellitus can be made based upon:

• Random plasma glucose ≥200 mg/dl (11.1 mmol/L) and symptoms of diabetes (polyuria, polydipsia, ketoacidosis, or unexplained weight loss) OR

• Fasting plasma glucose* ≥126 mg/dl (6.9 mmol/L) OR

• Results of a 2-hour 75-gram oral glucose tolerance test*

≥200 mg/dl (11.1 mmol/L) OR

• Glycated hemoglobin* (A1C) ≥6.5% (46 mmol/mol)**

*These tests should be confirmed by a repeat test, on a different day, unless unequivocally high.

**An A1C level of ≥6.5% on 2 separate days is acceptable for diagnosis of diabetes [1B]. However, some individuals may have an A1C <6.5% with diabetes diagnosed by previously established blood glucose criteria. Therefore, presence of either criterion is acceptable for diagnosis. Those with an A1C of 5.7%-6.4% (39-46 mmol/mol) are considered to have prediabetes, and they are at high risk for developing diabetes. These patients should be treated with lifestyle changes and followed more frequently.

The A1C test should be performed in a laboratory using a method that is certified by the National Glycohemoglobin Standardization Program and standardized to the Diabetes Control and Complications Trial assay.

A point-of-care (POC) A1C is not acceptable for diagnosis of diabetes.

1.2.2 Hemoglobin A1C (A1C)

Diagnosis:

See above section on Diagnosis of Diabetes Mellitus.

1.2.2a Goals:

The A1C target goal should be individualized for each patient. A goal of <7.0% (53 mmol/mol) is chosen as a practical level for most patients to reduce the risk of long-term complications of diabetes. Achieving this goal is recommended if it can be done safely and practically [1B].

Alternative A1C goals may be set, based upon presence or absence of microvascular and/or cardiovascular complications, hypoglycemic unawareness, cognitive status, and life expectancy [1A]. For patients with longstanding type 2 diabetes (T2D) with preexisting cardiovascular disease (CVD), or high coronary artery disease (CAD) risk (diabetes plus 2

or more additional risk factors), consider revising A1C goals to avoid adverse consequences of tight glycemic control, eg hypoglycemia [1A].

Some clinicians may translate patients’ A1C level into their estimated average glucose level, based upon the work of the A1C Derived Average Glucose Study. This metric is also a valid tool that may be used to assess the response of patients to their diabetes treatment plan [1C].

Joslin’s A1C target goal for most patients is consistent with that of the American Diabetes Association (ADA). Other expert panels, such as the American Association of Clinical Endocrinologists, suggest that the A1C target goal should be <6.5% in those newly diagnosed with diabetes and without comorbidities. Recent recommendation of 7% to 8% for most individuals with T2D by the Ameican College of Physicians are not endorsed by us ( see caveats above).

1.2.2b Caveats:

The A1C may not reflect glycemic control in special patient populations, including pediatric and geriatric populations, patients with anemia or other blood disorders resulting in rapid turnover of red blood cells, in chronic liver and renal disease, following recent blood transfusions, or while patients are hospitalized. It is therefore important to interpret

A1C results accordingly when determining treatment plans and goals.

1.2.2c Monitoring:

Monitor the A1C 2-4 times a year as part of the scheduled medical visit [1C] to evaluate efficacy of the treatment plan. The A1C may be checked more frequently if the treatment program requires revision, or the advice regarding behavior changes needs reinforcement. Having the A1C result at the time of the visit can be useful in making timely treatment decisions [1C].

Alternatively, the A1C may be performed prior to the medical visit POC method.

1.2.2d Treatment:

If A1C is ≥7% and <8%, or above the individualized goal, for 6 or more months:

• Review and clarify the management plan with the patient with special attention given to address:

-- nutrition and meal planning

--physical activity

-- medication administration,

schedule, and technique

-- self-monitoring blood glucose (SMBG) schedule and technique

-- treatment of hypoglycemia and hyperglycemia

-- sick day management practices

• Reassess goals and adjust medication as needed [1A]

• Establish and reinforce individualized glycemic goals with patient

• Refer patient to a certified diabetes educator (CDE) for evaluation, diabetes self-management education (DSME), and support for ongoing consultation [1C]

• Consider referral to RD for medical nutrition therapy (MNT) [1B]

• Schedule follow-up appointment within 3-4 months or more frequently as the situation may dictate

If A1C is ≥8%:

• Review and clarify the plan as previously noted

• Assess for psychosocial stress as a potential barrier to adequate response to treatment [1C]

• Establish and reinforce individualized glycemic goals with the patient

• Intensify therapy

• Refer patient to DE for evaluation, DSME, and support for ongoing consultation. Document reason if no referral initiated

• Refer patient to RD for MNT [1C]

If the patient has a history of severe recurrent hypoglycemia or hypoglycemia unawareness (a condition in which the patient is unable to recognize symptomsof hypoglycemia):

• Assess for changes in daily routine such as reduced food intake or increased physical activity [1C]

• Refer to DE for evaluation, DSME, and hypoglycemia prevention; encourage family/friend attendance

• Review use of glucagon

• Consider revising A1C goal

• Discuss and reinforce goals with patient

• Adjust medications to minimize hypoglycemia risk [1B]

• If insulin-treated, consider use of a more physiologic insulin replacement program, such as basal/bolus therapy

• Consider and screen for other medical causes

• Consider referral for blood glucose awareness training, if available

• Consider use of continuous glucose monitoring [2B]

1.3.0 SELF-MONITORING OF BLOOD GLUCOSE

• Schedule follow-up appointment within 1-2 months. If history of recent, severe hypoglycemia, or change in pattern of hypoglycemia, recommend increase in frequency of communicating blood glucose levels to provider or DE.SMBG is an important element of the treatment program for all individuals with diabetes. Its benefits are: to gauge treatment efficacy, to help in treatment design, to provide

feedback on the impact of nutritional intake and activity, to provide patterns that assist in medication selection, and, for those on insulin, to assist in daily dose adjustments [1B].

1.3.1 Goals:

Goals for glycemic control for most individuals with diabetes are:

• Fasting glucose: 80 to130 mg/dl (4.4-7.2 mmol/L)

• 2-hour postprandial glucose: <180 mg/dl (9.9 mmol/L)

• Bedtime glucose: 90 to 150 mg/dl (4.9-8.3 mmol/L)

1.3.2 Frequency:

The frequency of SMBG should be individualized, based on factors such as glucose goals, medication changes, and patient motivation. Most patients with type 1 diabetes (T1D)

should monitor 4 to 6 times per day. Some patients may need to monitor even more frequently.

Most patients using intensive insulin therapy should ideally monitor before meals and bedtime, prior to exercise, when they suspect hypoglycemia, after treating hypoglycemia, and prior to driving. In patients with T1D, there is a correlation between increased SMBG frequency and lower A1C. For patients with T2D, the frequency of monitoring is dependent upon such factors as mode of treatment and level of glycemic control [1C].

1.3.3 Postprandial monitoring:

To obtain meaningful data for treatment decisions, it is helpful for the patient to monitor for several consecutive days (eg, 2-4 days). In addition to obtaining fasting and preprandial glucose levels, consider obtaining glucose readings 2 to 3 hours postprandial, as postprandial hyperglycemia has been implicated as an additional cardiovascular risk factor [1B].

Postprandial monitoring is particularly recommended for patients who:

• Have an elevated A1C but fasting glucose is at target

• Are initiating intensive (physiologic) insulin treatment programs

• Are experiencing problems with glycemic control

• Are using glucose-lowering agents targeted at postprandial glucose levels

• Are making meal planning or activity adjustments

One-hour postprandial glucose monitoring should be considered:

• During pregnancy [1A]

• For those patients using alpha-glucosidase inhibitors

Encourage the patient to provide SMBG results (written records or meter for downloading) to each visit for review with provider/educator.

1.3.4 Using alternate sites to monitor:

Blood glucose levels from sites such as the upper arm, forearm, and thigh may lag behind those taken from the fingertips, particularly when glucose levels are changing

rapidly. Glucose levels may change rapidly with exercise, eating, or hypoglycemia, or after insulin administration. For this reason, alternate site monitoring is not recommended in

the following situations:

• When the blood glucose may be changing rapidly

• For patients using intensive insulin treatment programs

• If hypoglycemia is suspected

• In patients with hypoglycemia unawareness

1.3.5 Continuous glucose monitoring (CGM):

CGM measures interstitial glucose levels and correlates with plasma glucose levels. CGM requires calibration with SMBG at least twice daily. Use of CGM technology has been shown to decrease A1C in adults aged 25 years older using intensive insulin therapy along with CGM, compared with those using intensive insulin therapy with SMBG. The best predictor of A1C lowering was increased frequency of sensor use. CGM can be helpful in insulin-treated patients with hypoglycemia unawareness and/or frequent severe hypoglycemic episodes. The FDA has approved the use of properly calibrated CGM devices (ie, Medtronic 670G pump/sensor and Dexcom G6 sensor) to help make treatment decisions.

1.4.0 HYPOGLYCEMIA

1.4.1 Classification:

Patients with insulin-treated diabetes aged more than 65 years who would benefit from CGM should have access to it with insurance coverage. Intensive diabetes education and support are essential for optimal CGM implementation and ongoing use.

Prompt action is recommended for the treatment of hypoglycemia. When possible, the patient should confirm symptoms with SMBG to document hypoglycemia. All patients with T1D should ensure that a family member/companion/caregiver knows how to administer a glucagon injection in the event that the patient is unable or unwilling to take carbohydrate orally [1C].

The International Hypoglycemia Study Group recently recommended that hypoglycemia be classified as:

• Level 1 (glucose alert level) with glucose less than 70 mg/dL (3.8 mmol/L), which is considered sufficiently low for treatment with fast-acting carbohydrates

• Level 2 (clinically significant hypoglycemia) with glucose less than 54 mg/dL (2.9 mmol/L), which is considered serious and clinically important hypoglycemia

• Level 3 (severe hypoglycemia) with no specific glucose threshold but associated with cognitive impairment requiring external assistance.

1.4.2 Treatment:

• Caution patient to avoid alternate site monitoring with blood glucose meter when hypoglycemic

• Treat as mild-to-moderate hypoglycemia if patient is symptomatic or unable to confirm hypoglycemia with SMBG, or if blood glucose levels are >54 mg/dl (2.9 mmol/L) and <70 mg/dL (3.8 mmol/L) and are <90 mg/dL (4.9 mmol/L) at bedtime or overnight

• To treat mild-to-moderate hypoglycemia (plasma glucose 54-70 mg/dL [3.8-2.9 mol/L] most times of the day and <90 mg/ dL (4.9 mmol/L) at bedtime or overnight), begin with 15-20 grams of carbohydrate (1/2 cup juice or regular soft drink; 3-4 glucose tabs) [1C]

• If glucose level is ≤54 mg/dl (2.9 mmol/L), consume 20-30 grams of carbohydrate [1C]

• Recheck blood glucose after 15 minutes [1B]

• Repeat hypoglycemia treatment if blood glucose does not return to normal range after 15 minutes [1C]

• Follow with additional carbohydrates if next meal is more than 1 hour away [1C]

• If hypoglycemia persists after 2 to 3 treatments, patient or companion should be instructed to contact their healthcare provider or seek emergency care

• In event of severe hypoglycemia (altered consciousness, unable to take carbohydrate orally, or requiring the assistance of another person) treat with glucagon and/or intravenous glucose [1C]

• For patients with hypoglycemia unawareness, the threshold for treatment of hypoglycemia needs to be individualized [1C]

• For patients using real-time CGM, check 15 minutes post treatment using a finger stick and not the sensor reading. Due to the physiologic lag between blood and interstitial glucose, the sensor will yield a lower result and can lead to overtreatment [1B]

• For patients with gastroparesis, treat hypoglycemia with oral glucose gel

• The patient’s treatment plan should be revised if hypoglycemic events are frequent, or if they have hypoglycemia unawareness

1.4.3 Education:

• Instruct the patient to obtain and wear or carry diabetes identification

• Instruct patient to carry treatment for hypoglycemia at all times

• Instruct all patients with T1D, and patients with T2D who are at risk for hypoglycemia, to check blood glucose before operating a motor vehicle or other potentially dangerous equipment. In addition, advise them to check blood glucose regularly if driving for 1 or more hours. Hypoglycemia should be treated immediately, and patients should not drive until their blood glucose has reached and remained at a safe range for at least 30 minutes and/or until cognitive function is restored [1B]

• Identify potential causes of hypoglycemia to prevent its occurrence [1C]

• Be clear in communicating modified treatment goals in individuals with hypoglycemia unawareness

• Glucagon injections should be prescribed to all patients with severe hypoglycemia. Education on its use should be provided to the patient and to their

1.5.0 DIABETES SELF-MANAGEMENT EDUCATION AND SUPPORT (DSME/S)

caregivers/family members if possible

Everyone with diabetes should receive DSME/S according to the National Standards for Diabetes Self-Management Education and Support, to facilitate knowledge and to implement

and sustain self-care skills and problem-solving [1B].

Critical time points recommended for DSME/S are:

• At diagnosis

• Annually for assessment of education, nutrition and emotional needs

• When new complicating factors arise

• When transitions in care occur

Multiple visits with a DE are recommended to evaluate progress toward goals [1B].

1.6.0 MEDICAL NUTRITION THERAPY (MNT)

Group education sessions are encouraged for cost effectiveness and efficiency of staff utilization. Group education is a benefit to patients as it allows them to share ideas and concerns and enables them to learn from one another [1B].

No one-size-fits-all eating pattern exists for individuals with diabetes. Patients with newly diagnosed diabetes should receive either individualized or group MNT, preferably by a

registered dietitian nutritionist who is knowledgeable and skilled in providing diabetes-specific MNT. MNT delivered by a registered dietitian is associated with an A1C decrease

of 0.3%-1% for those with T1D and 0.5%-2% for patients with T2D [1A]. Goals of MNT are to promote healthy eating patterns while addressing the unique nutrition needs of

each patient based on their personal preferences, cultural background, health literacy, barriers to change, and ability to make changes in their eating habits.

Weight management is important for overweight and obese individuals living with T1D and T2D. There is strong evidence that modest and persistent weight loss is beneficial to the management of T2D and can delay the progression from prediabetes to T2D.

1.7.0 PHYSICAL ACTIVITY

For further details please refer to Chapter 2.All adults should consult their healthcare provider and/or see an exercise physiologist to discuss a safe exercise program that is appropriate to their abilities [1C].

1.7.1 Physical activity for healthy adults:

• Physical activity should be an integral component of the diabetes care plan to optimize glucose control, decrease cardiovascular risk factors, and achieve or maintain optimal body weight [1A]

• A moderate-intensity aerobic (endurance) physical activity minimum of 30 minutes 5 days per week or vigorous-intensity aerobic physical activity for a minimum of 20 minutes 3 days per week should be achieved unless contraindicated. Activity can be accumulated toward the 30-minute minimum by performing bouts, each lasting 10 or more minutes [1A]

• All adults, and particularly those with T2D, should decrease the amount of time spent in daily sedentary behavior. Prolonged sitting should be interrupted every 30 minutes for blood glucose benefits, particularly in adults with T2D.

• A target of 60 to 90 minutes of activity, 6 to 7 days per week, is encouraged for weight loss if overweight or obese [1A]

• To increase lean body mass, full body resistance training should be incorporated into the activity plan 3 to 4 days per week. It should include upper-body, core, and lower-body strengthening exercises using free weights, resistance machines, or resistance bands [1B]. Beginning training intensity should be moderate, involving 10 to 15 repetitions per set, with

increases in weight or resistance undertaken with a lower number of repetitions (8-10) only after the target number of repetitions per set can consistently be exceeded; increase in resistance can be followed by a greater number of sets and, lastly, by increased training frequency

• Stretching exercises should be done when muscles are warm or at the end of the activity plan to loosen muscles and prevent soreness [1B]

1.7.2 Physical activity for adults with medical or physical limitations:

• A moderate-intensity aerobic (endurance) physical activity minimum of 30 minutes, 5 days per week, or vigorous-intensity aerobic physical activity for a

minimum of 20 minutes, 3 days per week, should be achieved, as feasible, unless contraindicated. Activity can be accumulated toward the 30-minute

minimum by performing bouts each lasting 10 or more minutes [1A]

• To increase lean body mass, resistance training should be incorporated into the activity plan 3 to 4 days per week, as feasible. It should include upper-body, core,

and lower-body strengthening exercises using free weights, resistance machines, or resistance bands [1B]

• Incorporate balance exercises to prevent falling and injury

• Functional Fitness Testing is useful to assess patients’ functionality and track their progress. Testing such as the 6-Minute Walk Test, 2-Minute Step Test, Balance

Assessment, and Hand Strength should be included at baseline and post intervention [1C]

1.8.0 CARDIOVASCULAR HEALTH

• See section on Ocular Health.(Also see sections on Lipids, Blood Pressure, Physical Activity, and Smoking)

1.8.1 Antiplatelet therapy:

A daily enteric-coated aspirin (ASA) (75-162 mg) unless contraindicated* as a primary prevention strategy for men aged ≥50 years [1C] and for women ≥60 years of age [1C] with

1 or more of the following risk factors:

• Family history of premature** CAD or stroke

• Hypertension (HTN)

• Current cigarette smoker

• Albuminuria

• Hyperlipidemia

Recommend a daily enteric-coated ASA (75-162 mg), or clopidogrel (75 mg, if aspirin-intolerant), or another agent of the class as a secondary prevention strategy for anyone with

1 or more of the following [1A]:

• History of myocardial infarction (MI), angina, or documented CAD

• Vascular revascularization

• Nonhemorrhagic stroke

• Transient ischemic attack

• Peripheral artery disease (PAD)

*Possible contraindications for antiplatelet therapy may include allergy, bleeding tendency, anticoagulant therapy, recent gastrointestinal bleeding, and clinically active hepatic disease.

Eye disease is usually not a contraindication for ASA therapy.

**Premature: 1st-degree male relative aged less than 55 years; 1st-degree female relative aged less than 65 years.

1.8.2 Other therapeutic considerations:

Consider using beta-blockers in all patients with a history of MI or with documented CAD unless contraindicated [1A]. Consider using angiotensin-converting-enzyme (ACE)

inhibitors (or angiotensin receptor blockers [ARBs] if ACE inhibitors not tolerated) in patients with known CAD or cardiovascular risk factors and aged ≥55 years [1B].

Thiazolidinediones (TZDs) (ie, pioglitazone, rosiglitazone) are contraindicated in patients with heart failure defined as New York Heart Association (NYHA) classes III and IV [and conditions of fluid overload (ie, congestive heart failure). See Clinical Guideline for Pharmacological Management of Adults With Type 2 Diabetes (Chapter 5) for additional caveats on TZDs [1A].

Consider recommending aerobic activity if not clinically contraindicated, and a weight-loss program if patient is overweight or obese. [1A]

1.8.3 When to conduct a stress test:

Based on current research and understanding of CAD in diabetes, it is reasonable to screen patients with diabetes who [1C]:

• Complain of typical or atypical chest pain

• Have an abnormal electrocardiogram (ECG)

• Have a diagnosis of PAD or carotid artery disease

• Are aged >35 years with sedentary lifestyle about to start a rigorous exercise program

Currently, no strong evidence supports screening asymptomatic patients with T2D for silent myocardial ischemia [1C].

Patients with autonomic neuropathy may have increased risk of asymptomatic ischemia and therefore warrant careful attention [1B].

If stress testing is performed, either nuclear imaging or echocardiography with ECG monitoring is recommended. An exercise stress test is preferred, if resting ECG is normal and

patient is able to exercise, because the response to exercise is an important prognostic factor. If the patient cannot adequately exercise, pharmacologic stress testing is warranted.

1.8.4 Lipid management:

1.8.4a Screening for lipid disorders:

Adults should be screened annually for lipid disorders with measurements of serum cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) and high-density

lipoprotein cholesterol (HDL-C), preferably fasting [1B].

1.8.4b Treatment:

All patients should receive information about a meal plan designed to improve glycemic and lipid control, physical activity recommendations, and cardiovascular risk reduction

strategies (with an emphasis on smoking cessation and blood pressure control). Consultation with appropriate education discipline is preferred [1A].

Institute therapy after abnormal values are confirmed.

• All patients with any form of clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD), or with LDL-C ≥190 mg/dl: Treat with statin to reduce

LDL-C ≥50% [1A]

• Patients aged 40 to 75 years without clinical evidence of ASCVD, with LDL-C 70-189 mg/dl: Treat with statin to reduce LDL-C by 30% to 49%. Consider reduction of ≥50% if 1 or more of the following additional major risk factors are present:

-- Calculated 10-year risk of ASCVD ≥7.5% using the American College of Cardiology/American Heart Association risk equation calculator (my.americanheart.org/cvriskcalculator) [1B]

-- Family history of premature ASCVD

-- High blood pressure

-- Tobacco use

-- AlbuminuriaIn patients aged <40 years, consider statin if LDL-C ≥100 mg/dl and multiple ASCVD risk factors are present [2B]

• In patients aged >75 years, no clear evidence exists for benefits of initiating statin therapy in the absence of ASCVD or multiple CV risk factors [2C]

• Recheck lipids after drug initiation or dose escalation in 6 to 12 weeks. Thereafter, check lipids every 3 to 12 months to monitor adherence. May down-titrate statin

dose if LDL-C <40 mg/dl

• No evidence exists for benefits of statin therapy in patients on hemodialysis or those with heart failure (NYHA class II-IV) [1B]

• If adequate reduction in LDL-C as described above has been achieved, a specific LDL-C goal (<70 and <100 mg/dl) or non-HDL-C goal (<100 and <130 respectively)

for those with or without ASCVD, respectively, is not recommended

• In patients with ASCVD or with familial hypercholesterolemia, who are unable to achieve LDL-C goal with maximum tolerated statin therapy, add ezetimibe and

consider a PCSK9 inhibitor

• For primary prevention of ASCVD, consider use of ezetimibe or bile acid sequestrant or niacin (alone, or in combination therapy) for patients intolerant

to multiple statins or who have unacceptable adverse events [2B]

• Statins are contraindicated during pregnancy or if contemplating pregnancy

Patients with LDL-C at goal and fasting triglycerides ≥150 mg/dl or HDL-C ≤40 mg/dl:

• Optimize glycemic control [1A]

• Refer to RD for dietary modification and therapeutic lifestyle changes [1A]

• Consider referral to an exercise specialist for an appropriate exercise regimen

• Recheck lipids within 6 to 12 weeks

• In patients with fasting triglyceride levels 200 to 499 mg/dl and/or HDL-C ≤35 mg/dl after optimal statin therapy; calculate non-HDL-C, intensify statin if

non-HDL-C not in goal before considering addition of fibrate [2B]

• If triglycerides are persistently ≥500 mg/dl, secondary causes of hypertriglyceridemia should be considered and managed appropriately.

Initiate treatment with a very low-fat meal plan and with a fibrate for prophylaxis against acute pancreatitis; reassess lipid status when triglycerides <500 mg/dl [1A]

• If fasting triglycerides remain ≥ 500 mg/dl after initiation of fibrate, consider the addition of fish oil (to provide 2 to 4 grams omega-3 fatty acids

daily) or niacin [2B]

1.8.5 Blood pressure management:

1.8.5a Blood pressure measurement:

• Check blood pressure (BP) at all routine visits after patient has been seated for at least 5 minutes. Use proper-size cuff and arm position. Postural BP (sitting, then standing) should be checked initially, and as clinically indicated:

-- In cases of known or suspected orthostatic hypotension (defined as a fall in systolic BP [SBP] of >20 mmHg or diastolic BP [DBP] of >10 mmHg or an increase in heart rate by more than 20 beats per minute after 3 minutes of standing)

-- In cases where standing upright is associated with lightheadedness, syncope, or signs of brain hypoperfusion [1C]

• Initiate lifestyle changes if BP >130/80 mm/Hg

• Consider initiating pharmacologic therapy if the average of 3 blood pressure measurements is >140/90 mmHg

• Schedule for follow-up blood pressure check within 1 month [1B]

1.8.5b Blood pressure targets:

• BP goal for each patient aged >18 years is ≤140/90 mmHg [1B] The recent recommendation for achieving BP target of < 130/80 by the American College of Cardiology and others is controversial in patients with diabetes and not endorsed by the Joslin Clinical Oversight Committee or the ADA.

• SBP <130 mmHg may be appropriate for individuals without CVD or without multiple risk factors [1B]

• No clear evidence exists for significant benefits to be gained by lowering SBP to <120 mmHg in those with coronary heart disease or multiple risk factors [1B]

• BP goal for patients with albuminuria ≥300mcg/mg is <130/80 mmHg, if tolerated [1C]

• Initial goal for patients with isolated systolic HTN (SBP >180 mmHg and DBP <80 mmHg) is a SBP <160 mmHg [2B] or < 140 mmHg if safely achieved.

• Initial goal for patients with SBP 160-179 mmHg is to lower SBP by 20 mmHg. If well tolerated, lower BP goals may be indicated [1B]

1.8.5c Treatment:

If SBP ≥140 mmHg or DBP ≥90 mmHg, a 3-month trial of lifestyle modification is warranted as follows [1C]:

• Counsel about meal plans, use of Dietary Approaches to Stop Hypertension (DASH), the DASH low-sodium diet, and sodium reduction in general. Also, counsel about activity, weight loss, alcohol use, and stress reduction

• Consider referral to RD for MNT

• Encourage home BP self-monitoring and providing documentation during clinic visits

• Instruct patient to have BP checked 2 times a week prior to the next appointment

• Follow-up with healthcare provider within 2 to 4 weeks

• Initiate or adjust therapy with antihypertensive agents as clinically indicated if BP remains above goal

Studies have shown that aggressive management and control of BP may result in long-term benefits.

• Pharmacotherapy:

Efficaciousness is the most important consideration in choosing an initial antihypertensive drug. In that sense, any available antihypertensive drug can be an appropriate

choice. However, other considerations (eg, presence of albuminuria, coexisting CAD, cost) may dictate a preference for an ACE inhibitor, ARB, calcium channel

blocker, or thiazide-type diuretic [1A]. In general, ACE inhibitors and ARBs should not be used in combination.

Consider ACE inhibitors or ARBs for patients with persistent urine albumin/creatinine ratio ≥30 mcg/mg. These drugs require monitoring of serum creatinine and K+ within 1 week of

starting therapy and periodically thereafter [1A]. (See section on Renal Health.)

1.9.0 RENAL HEALTH

1.9.1 Screening for renal health:

ACE inhibitors/ARBs are contraindicated during pregnancy or if contemplating pregnancy.

Measure serum creatinine at least annually to estimate glomerular filtration rate (eGFR) regardless of degree of urine albumin excretion.) [1C]

Measure eGFR using chronic kidney disease epidemiology (CKD-EPI) calculation.

If eGFR is <60 ml/min, evaluate for complications of kidney disease (anemia, hyperparathyroidism, and vitamin D deficiency).

Screen for albuminuria by checking urine albumin/creatinine (A/C) ratio as follows:

• Patients with T1D within 5 years after diagnosis and then yearly [1C]

• Patients with T2D at diagnosis (after glucose has been stabilized) and then yearly [1C]

• Annually in all patients up to age 70 years [2C]

• As clinically indicated in patients aged >70 years

Albuminuria is recognized as a major independent risk factor for CAD in patients with diabetes. Albuminuria may be measured with a spot or timed urine collection. Spot urine is

preferred for simplicity.

Continue use of routine urinalysis as clinically indicated [2C].

Patients should be advised that BP control, glycemic control, and management of albuminuria may slow the progression of CKD.

1.9.2 Evaluation and treatment of diabetes kidney disease (DKD)

If A/C ratio <30 mcg/mg or timed urine albumin <30 mg/24 hours:

• recheck in 1 year

If A/C ratio 30-299 mcg/mg or timed urine albumin 30-299 mg/24 hours:

• Confirm presence of albuminuria with at least 2 of 3 positive collections done within 3-6 months. In the process, rule out confounding factors that cause a false

positive, such as urinary tract infection, pregnancy, excessive exercise, menses, or severe hypoglycemic event [1C]

• Consider testing first morning urine

• Consider consult with nephrologist for blood pressure control, successive increases in albumin, and other issues (ie, eGFR <60 ml/min) [2C]

Once DKD confirmed:

• Evaluate BP and initiate/modify aggressive blood pressure treatment to achieve a BP of <130/80 mmHg [2B]

• Recommend that patient self-monitor BP with portable cuff and maintain a record/log. The monitoring schedule should be determined with the healthcare provider and is based on patient circumstance

• Strive to improve glycemic control with an optimal goal A1C of <7% or as otherwise clinically indicated [1A]

• Refer to DE for glucose management

• Initiate/modify ACE inhibitor or ARB treatment if albuminuria persists. Check K+ and creatinine about 1 week after making these medication changes [1A]

• Repeat A/C ratio at least every 6 months. Consider increase in frequency when changes in medication are made [2C]

If A/C ratio ≥300 mcg/mg (≥300 mg/24 hours) or persistent albuminuria presents (positive dipstick for protein or ≥30 mg/dl):

• Follow all guidelines as stated for A/C ratio 30-300 mcg/mg

• Consider BP goal of <130/80 mmHg [2B]

• Evaluate for patient adherence, with emphasis on avoidance of high sodium and of very high protein intake

• Consider referral to RD for MNT

• Consider referral to nephrologist to:

• Assess cause(s) of impaired kidney function, including assessing for DKD

• Maximize therapies aimed at slowing progression

of kidney disease (eg, BP control; reduction of

urine protein level)

• Treat complications of kidney disease (hyperphosphatemia,

anemia, etc)

• Evaluate any rapid rise in serum creatinine, abnormal sediment, or concomitant hematuria, or sudden increase in albuminuria

• Assess problems with ACE inhibitor use and difficulties in management of high BP or hyperkalemia

Manage resistant hypertension, defined as BP that remains above goal despite concurrent use of 3 antihypertensive agents of different classes (1 of which should

1.10.0 OCULAR HEALTH

1.10.1 Screening for eye disease:

be a diuretic. All should be at maximum dose tolerated)

Refer patient for comprehensive dilated eye exam or validated retinal imaging to determine level of retinopathy.

• T1D: initial eye exam at start of puberty or once patient is 10 years of age or older, whichever is earlier, within 3 to 5 years of diagnosis. Annual eye exam thereafter [1A]

• T2D: at diagnosis and annually thereafter [1A]

• Pregnancy in woman with preexisting diabetes: several exams, including prior to conception; during first trimester; follow-up during pregnancy as determined by first-trimester exam; and 6 to 12 weeks postpartum [1B]

• For physiologic insulin therapy (pump therapy or multiple daily injections): Consult with patient’s eye care provider or evaluate retinal status with validated retinal imaging to determine level of retinopathy and appropriate follow-up care prior to initiating physiologic insulin therapy [1A]

1.10.2 Treatment:

Aggressively treat known medical risk factors for onset and progression of retinopathy:

• Strive to improve glycemic control with optimal A1C goal of <7% [1A]

• Monitor eye disease carefully when intensifying glycemic control [1A]

• Strive for BP <130/80 mmHg [1B]

• Treat albuminuria [1B]

• Strive to maintain total cholesterol, LDL-C, HDL-C, and triglyceride levels as per the recommendations outlined in the Lipids section of this guideline [1A]

• Treat anemia [1B]

Activity programs that involve strenuous lifting; harsh, high-impact components; or activities that place the head in an inverted position for extended periods of time may need

to be revised depending on the level of retinopathy.

Reinforce follow-up with eye-care provider for any level of retinopathy, including no apparent retinopathy. The frequency of follow-up is dependent upon the level

of retinopathy and presence of risk factors for onset and progression of retinopathy and is determined by the eye care provider.

• For high-risk proliferative diabetic retinopathy, prompt scatter (panretinal) laser photocoagulation and/or intravitreal anti—vascular endothelial growth factor

(VEGF) injection is indicated [1A]

• For clinically significant macular edema (CSME) or center-involved macular edema, focal laser and/or intravitreal anti-VEGF injection is generally indicated

regardless of level of retinopathy [1A]

• The level of diabetic retinopathy and diabetic macular edema (DME) generally determines follow-up* [1A].

See suggested follow-up time spans below:

If No Diabetic Retinopathy:

• 12 months

If Mild Nonproliferative Diabetic Retinopathy:

• Without DME, 12 months

• With DME,** monthly if undergoing anti-VEGF treatment, otherwise 3 to 4 months

If Moderate Nonproliferative Diabetic Retinopathy:

• Without DME, 6 to 9 months

• With DME,** monthly if undergoing anti-VEGF treatment, otherwise 3 to 4 months

If Severe-to-Very Severe Nonproliferative Diabetic Retinopathy:

• Without DME,*** 3 to 4 months

• With DME,** monthly if undergoing anti-VEGF treatment, otherwise 3 to 4 months

If Proliferative Diabetic Retinopathy Less Than High-Risk:

• Without DME,*** 1 week to 3 to 4 months

• With DME,** 1 week to 1 month if undergoing anti-VEGF treatment, otherwise 3 to 4 months

If High-Risk Proliferative Diabetic Retinopathy:

• With or without DME: scatter (panretinal) laser photocoagulation and/or intravitreal anti-VEGF injection with follow-up in 3 months, or 1 month and monthly thereafter if undergoing anti-VEGF treatment

*The presence of known risk factors for onset and progression of retinopathy may suggest follow-up at shorter intervals for all levels of retinopathy.

**Focal laser surgery and/or intravitreal anti-VEGF injection is generally indicated for CSME or center-involved macular edema. If receiving anti-VEGF treatment, follow-up

is generally monthly.

1.11.0 NERVOUS SYSTEM HEALTH

1.11.1 Screening for neuropathy

1.11.1a Methods:

***Scatter laser surgery may be indicated, especially for T2D or T1D of long duration

• Ask patient about loss of sensation in the limbs, symptoms of pain, tingling, paresthesia, weakness, or gait instability.

• Evaluate feet for sensation using a 128 Hz tuning fork and Semmes-Weinstein 5.07 monofilament [1B]

• Evaluate reflexes

• Laboratory screening with complete blood count, lipid panel, thyroid panel, B12 level (methylmalonic acid and/or homocysteine if low-normal B12),

and serum and urine protein electrophoresis, as clinically indicated

Neurophysiologic testing (electromyogram, nerve conduction studies, or skin biopsy analysis of intra-epidermal nerve fiber density) should be considered in atypical cases

• Assess for symptoms of autonomic neuropathy such as erectile dysfunction, gastroparesis, or postural hypotension. If symptoms of autonomic neuropathy are present, refer for evaluation by formal autonomic testing (including heart rate variability testing, blood maneuver, and the blood pressure response to upright tilt table testing or standing) [1B]

1.11.1b Frequency:

• For patients with T1D and T2D without complications, conduct symptom and examination screen at time of diagnosis and at least annually [1C]

• For “at-risk patients,”* conduct symptom and examination screen at all routine interval visits [1C]

• Laboratory screening at the time of diagnosis of diabetes or with change in symptoms or examination [1C]

• Screen for cardiovascular autonomic neuropathy at the time of diagnosis of T2D, or 5 years after diagnosis of T1D. Screening should be repeated yearly or

with development of symptoms [1C]. If symptoms of autonomic neuropathy are present, refer for evaluation by formal autonomic testing (including

heart rate variability testing, blood pressure and heart rate response to a Valsalva maneuver, and the blood pressure response to upright tilt table testing

or standing) [1B]

• Neurophysiologic testing only for atypical cases [1C] *“At-risk patients” include patients who smoke; who have vascular insufficiency, neuropathy, retinopathy, nephropathy,

structural deformities, infections, skin/nail abnormalities, or a history of ulcers or amputations; who are on anticoagulation therapy; or who cannot see, feel, or reach their feet.

1.11.2 Treatment:

For patients with acute problems or who are “at risk”:

• Consider referral to neurologist for:

-- atypical neuropathy

-- rapidly progressive symptoms

-- severe pain unresponsive to first-line therapy

-- weakness suggestive of diabetic amyotrophy

For patients with symptoms related to diabetic peripheral or autonomic neuropathy:

• Consider medications, because they improve quality of life [1A]

1.12.0 FOOT HEALTH

1.12.1 Screening

1.12.1a Methods:

•

Screening should include:

• Questions about loss of sensation in the limbs, or symptoms of pain, including claudication, tingling, or other paresthesia

• Foot evaluation for sensory function (Semmes-Weinstein 5.07 monofilament and 128 Hz tunic fork) [1B]

• Evaluation of reflexes, skin and soft-tissue integrity, nail condition, callous formation, vascular sufficiency (pedal pulses), and biomechanical integrity

• Examination of shoes for wear and appropriateness

1.12.1b Frequency:

• For patients with T1D and T2D without complications or significant risk factors, conduct foot screen at time of diagnosis and at least annually thereafter [1C]

• For “at-risk patients,”* check feet at all routine interval visits [1C]

*“At-risk patients” include patients who smoke; who have vascular insufficiency, neuropathy, retinopathy, nephropathy, structural deformities, infections, skin/nail abnormalities, or a

history of ulcers or amputations; who are on anticoagulation therapy; or who cannot see, feel, or reach their feet.

1.12.2 Treatment:

For patients with acute problems or who are “at risk”:

• Refer to podiatric physician for routine care and evaluation [1B]

• Refer to DE for foot care training** [1C]

• Consider referral to neurologist for:

-- atypical neuropathy

-- rapidly progressive symptoms

-- severe pain unresponsive to first-line therapy

-- weakness suggestive of diabetic amyotrophy

For mild current ulcer or infection** [1C]

** Mild ulcer or infection is characterized by: (a) superficial lesion (no foul odor), (b) no significant ischemia, (c) no bone or joint involvement, (d) no systemic toxicity, (e) minimal or no cellulitis (<2 cm)

• Instruct patient in nonweight-bearing, if appropriate

• Apply local dressings with topical antiseptic

• Consider baseline x-ray to evaluate for bone integrity

and possible osteomyelitis

• Consider systemic antibiotic therapy

• Refer to podiatric physician for evaluation

and treatment

• Refer to DE for foot-care training

• Ensure follow-up appointments are kept

For limb-threatening*** ulcer or infection [1C]:

***Limb-threatening ulcer or infection is characterized by (a) deep ulcer, (b) bone or joint involvement, (c) gangrene, (d) lymphangitis, (e) cellulitis (>2 cm), (f) systemic toxicity, (g) significant ischemia, (h) no social support system, (i) immunocompromised, (j) foul odor in ulcer.

Osteomyelitis is presumed to be present if able to probe through the ulcer to the bone.

• Urgent hospitalization

• Consult a podiatric physician and vascular surgeon for immediate evaluation and treatment

• Foot care training should address:

-- Avoidance of foot trauma

-- Daily foot inspection

-- Nail care

-- Callous formation

-- Proper footwear

-- Impact of loss of protective sensation on morbidity

-- Need for smoking cessation

-- Action to take when problems arise

1.13.0 ORAL HEALTH

-- Importance of glucose control on disease progression• Periodontal disease is associated with suboptimal diabetes control and may be a risk factor for cardiovascular disease. There is mixed evidence on the impact of treatment of periodontal disease on glycemic control

• Referral to a dentist should be considered an essential component of a comprehensive diabetes care plan

• At initial visit and annually, discuss need for dental cleaning at least every 6 months [1C]

• Refer to dental specialist for oral symptoms and findings such as sore, swollen, or bleeding gums, loose teeth, or persistent mouth ulcers [1C]

1.14.0 BEHAVIORAL HEALTH

• If edentulous, refer to dental specialist for restoration of functional dentitionA psychosocial evaluation should be an integrated component of the initial assessment and the ongoing care of all patients with diabetes and should be strongly considered in

the following situations:

Newly diagnosed diabetes:

• Assess at least the following [1C]:

• Ability to cope with the emotional impact and lifestyle changes of diabetes

• Level of social support

• Barriers to treatment and self-management

• Type and degree of nondiabetes-related life stress

During hospitalizations or any intensification in treatment, significant life change, problems with self-management, or metabolic stability. Key areas to assess:

• Diabetes distress: consider using Problem Areas in Diabetes as a screening tool.

• Depression: consider using Patient Health Questionnaire (PHQ)-2 or PHQ-9 as a screening tool

• Anxiety (eg, compulsive SMBG fear of injections).

• Exaggerated fear of hypoglycemia: Consider referral for blood glucose awareness training.

• Disordered eating: Consider inquiry about insulin omission or bingeing if A1C >9% or diabetic ketoacidosis is recurrent

• Family conflict related to diabetes

• Substance abuse: Consider use of the CAGE alcohol screening tool

Newly diagnosed complications from diabetes. Assess at least the following:

• Emotional impact (diabetes distress, depression,

anxiety) and lifestyle changes for patient and family

• Barriers to treatment and self-management

• Level of social support

• Type and quantity of nondiabetes-related life stress

1.15.0 WOMEN’S HEALTH

Patients using second-generation or atypical antipsychotic medications should be monitored for weight gain with resulting increases in glucose, lipid, and blood pressure levels.(Refer to Joslin Guideline for Detection and Management of Diabetes in Pregnancy [Chapter 3]).

• All women of reproductive age should be assessed for the possibility of pregnancy prior to initiating new medications, and they should be counseled on potential risks to the developing fetus.

• Counsel women with the potential for conception about contraception use and relationship of blood glucose control to fetal development and pregnancy outcomes [1C]

• At initial and annual visit, discuss sexual function -- Assess for infectious, hormonal, psychological, or structural etiologies if dysfunction exists

-- Refer to specialist as indicated [1C]

• Follow appropriate guidelines for pap/pelvic and mammography screening for primary care patients [1B]

• Individualize approach to bone health for women with risk factors for osteoporosis, including surgical and natural menopause [1B]

1.16.0 MEN’S HEALTH

-- Ensure adequate intake of calcium and vitamin D• At initial and annual visit, discuss sexual function and any fertility concerns -- Assess for hormonal, psychological, or structural etiologies if dysfunction exists [1C]

• For men with type 2 diabetes, consider screening for low testosterone [1B]

-- Screen for total testosterone and sexhormone—binding globulin

1.17.0 ADDITIONAL CONSIDERATIONS

1.17.1 Tobacco dependence:

• Refer to specialist as indicated

Screen: Assess patient’s use of tobacco and e-cigarettes at initial and follow-up visits.

Treatment (if patient smokes)

• Discuss rationale for and strongly recommend smoking cessation [1A]

• Review options available to assist in smoking cessation, including medications and cessation programs [1B]

1.17.2 Identifying sleep disorders:

• At initial visit and annually, inquire about sleep quality, level of fatigue, and symptoms such as snoring and restless sleep [1C]

• Obstructive sleep apnea is more frequent in the setting of central obesity and is a risk factor for ASCVD

• Refer for sleep study if indicated

• The evidence surrounding the impact of sleep apnea treatment on diabetes control has been so far inconclusive

• Pay special attention to shift workers. An individualized care plan should be tailored to their schedules, and the effect of shift work on glycemic control should

be assessed at each visit

1.17.3 Immunizations:

Recommend the following vaccines:

• Influenza vaccine: yearly for all adult patients with diabetes [1B]

• Pneumococcal vaccine with pneumococcal polysaccharide vaccine (PPSV23): once for all patients with diabetes [1B]

-- Patients ≥65 years of age should receive pneumococcal conjugate vaccine (PCV13) at least 1 year after vaccination with PPSV23, followed by a 1-time revaccination

if they received the previous dose ≥5 years earlier [1C]

-- Repeat vaccination should be considered for those with nephrotic syndrome, chronic renal disease, and other immunocompromised states

-- Hepatitis B Vaccine 3-dose series: for unvaccinated adult patients with diabetes (age 19-59 years) [1C]. May also consider for unvaccinated adults ≥60 years [2C]

Address Correspondence to:

Om P. Ganda, MD

1 Joslin Place

Boston, MA 02215

Phone: 617-309-2645

Email: om.ganda@joslin.harvard.eduReferences

Approach to Care

1. American Diabetes Association. Standards of medical care in diabetes 2018 Diabetes Care 2018; 41(suppl1): S13-S27. doi:10.2337/dc18-3002.

2. Beck J, Greenwood DA, Blanton L, et al. 2017 National Standards for Diabetes Self-Management Education and Support. Diabetes Spectr 2017;30:301-14.

3. Deakin T, McShane CE, Cade JE, Williams RD. Group-based training for self-management strategies in people with type 2 diabetes mellitus. Cochrane Database Syst Rev.

2005;(2):CD003417.4.

4. American Diabetes Association; Lorber D, Anderson J, Arent S, et al. Diabetes and driving. Diabetes Care. 2012;35(suppl 1):S81-S86. doi: 10.2337/dc12-s081.

5. Nathan DM, Balkau B, Bonoro E, et al; International Expert Committee. International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes.

Diabetes Care. 2009;32(7):1327-1334. doi: 10.2337/dc09-9033.

6. Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and high risk for diabetes using A1C criteria in the U.S. population in 1988-2006. Diabetes Care.

2010;33(3):562-568. doi: 10.2337/dc09-1524.

7. Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ; A1c-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose

values. Diabetes Care. 2008;31(8):1473-1478. doi: 10.2337/dc08-0545.

8. Beck RW, Connor CG, Mullen DM, Wesley DM, Bergenstal RM. The fallacy of average: How using HbA1c alone to assess glycemic control can be misleading. Diabetes Care

2017;40:994-999.

Glucose Monitoring

9. Hirsch IB, Bode BW, Childs BP, et al. Self-monitoring of blood glucose (SMBG) in insulin- and non-insulin-using adults with diabetes: consensus recommendations

for improving SMBG accuracy, utilization, and research. Diabetes Technol Ther. 2008;10(6):419-439. doi: 10.1089/dia.2008.0104.

10. Saudek CD, Derr RL, Kalyani RR. Assessing glycemia in diabetes using self-monitoring blood glucose and hemoglobin A1C. JAMA. 2006;295(14):1688-1697.

11. Welschen LM, Bloemendal E, Nijpels G, et al. Self-monitoring of blood glucose in patients with type 2 diabetes who are not using insulin: a systematic review. Diabetes

Care. 2005;28(6):1510-1517. doi: 10.2337/diacare.28.6.1510.

12. Miller KM, Beck RW, Bergenstal RM, et al; T1D Exchange Clinic Network. Evidence of a strong association between frequency of self-monitoring of blood glucose and

hemoglobin A1c levels in T1D Exchange Clinic registry participants. Diabetes Care. 2013;36(7):2009-2014. doi: 10.2337/dc12-1770.

13. American Diabetes Association. Standards of medical care in diabetes 2017. 6. glycemic targets [published correction appears in Diabetes Care. 2017;40(7):985].Diabetes

Care. 2017;40(suppl 1):S48-S56. doi: 10.2337/dc17-S009.

14. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Tamborlane WV, Beck RW, Bode BW, et al. Continuous glucose monitoring

and intensive treatment of type 1 diabetes. N Engl J Med. 2008;359(14):1464-1476. doi:10.1056/NEJMoa0805017.

15. Peters AL, Ahmann AJ, Battelino T, et al. Diabetes technology—continuous subcutaneous insulin infusion therapy and continuous glucose monitoring in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(11):3922-3937. doi: 10.1210/jc.2016-2534.

16. Choudhary P, Ramasamy S, Green L, et al. Real-time continuous glucose monitoring significantly reduces severe hypoglycemia in hypoglycemia-unaware patients with

type 1 diabetes. Diabetes Care. 2013;36(12):4160-4162. doi: 10.2337/dc13-0939.

17. Beck RW, Riddlesworth T, Ruedy K, et al; DIAMOND Study Group. Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin

injections: the DIAMOND randomized clinical trial. JAMA. 2017;317(4):371-378. doi:10.1001/jama.2016.19975.

18. Beck RW, Riddlesworth TD, Ruedy K, et al. Continuous Glucose Monitoring Versus Usual Care in Patients With Type 2 Diabetes Receiving Multiple Daily Insulin Injections:

A Randomized Trial. Ann Intern Med 2017;167:365-74.

Hypoglycemia

19. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003;26(6):1902-1912. doi: 10.2337/diacare.26.6.1902.

20. Cox DJ, Kovatchev BP, Koev D. et al. Hypoglycemia anticipation, awareness and treatment training (HAATT) reduces occurrence of severe hypoglycemia among adults

with type 1 diabetes mellitus. Int J Behav Med. 2004;11(4):212-218. doi: 10.1207/s15327558ijbm1104.

21. Brackenridge A, Wallbank H, Lawrenson RA, Russell-Jones D. Emergency management of diabetes and hypoglycaemia. Emerg Med J. 2006;23(3):183-185. doi: 10.1136/

emj.2005.026252.

22. Heller SR. Minimizing hypoglycemia while maintaining glycemic control. Diabetes. 2008;57(12):3177-3183. doi: 10.2337/db08-1195.

23. Cryer PE. Hypoglycemia: still the limiting factor in the glycemic management of diabetes. Endocr Pract. 2008;14(6):750-756. doi: 10.4158/EP.14.6.750.

24. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological

analysis of the ACCORD study. BMJ. 2010;340:b4909. doi: 10.1136/bmj.b4909.

25. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes

Care. 2013;36(5):1384-1395. doi: 10.2337/dc12-2480.

26. International Hypoglycemia Study Group. Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: a joint position statement

of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2017;40(1):155-157. doi: 10.2337/dc16-2215.

Diabetes Self-Management Education (DSME) and Medical Nutrition Therapy (MNT)

27. American Diabetes Association. Standards of medical care in diabetes 2017. 4. lifestyle management. Diabetes Care. 2017;40(suppl 1):S33-S43. doi: 10.2337/dc17-S007.

28. Evert AB, Boucher JL, Cypress M, et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2014;37(Suppl 1):S120-S143. doi:

10.2337/dc14-S120.

29. Haas L, Maryniuk M, Beck J, et al; 2012 Standards Revision Task Force. National standards for diabetes self-management education and support. Diabetes Care.

2014;37(suppl 1):S144-S153. doi: 10.2337/dc14-S144.

30. Franz MJ, Monk A, Barry B, et al. Effectiveness of medical nutrition therapy provided by dietitians in the management of non-insulin-dependent diabetes mellitus: a

randomized controlled clinical trial. J Am Diet Assoc. 1995;95(9):1009-1017. doi:10.1016/S0002-8223(95)00276-6.

31. Lemon CC, Lacey K, Lohse B, Hubacher DO, Klawitter B, Palta M. Outcomes monitoring of health, behavior, and quality of life after nutrition intervention in adults with type 2

diabetes. J Am Diet Assoc. 2004;104(12):1805-1815. doi: 10.1016/j.jada.2004.09.024.

32. Miller CK, Edwards L, Kissling G, Sanville L. Nutrition education improves metabolic outcomes among older adults with diabetes mellitus: results from a randomized

controlled trial. Prev Med. 2002;34(2):252-259. doi: 10.1006/pmed.2001.0985.

33. Pastors JG, Franz MJ, Warshaw H, Daly A, Arnold MS. How effective is medical nutrition therapy in diabetes care? J Am Diet Assoc. 2003;103(7):827-831.

34. Powers MA, Bardsley J, Cypress M, et al. Diabetes self-management Education and Support in Type 2 Diabetes: a joint position statement of the American Diabetes

Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics. Diabetes Care. 2015;38(7):1372-1382. doi: 10.2337/dc15-0730.

35. Mozaffarian D. Dietary and policy priorities for cardiovascular disease, diabetes and obesity. a comprehensive review. Circulation. 2016;133(2):187-225. doi: 10.1161/

CIRCULATIONAHA.115.018585.

Physical Activity

36. Haskell WL, Lee IM, Pate RR, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the

American Heart Association. Med Sci Sports Exerc. 2007;39(8):1423-1434. doi: 10.1249/mss.0b013e3180616b27.

37. Nelson ME, Rejeski WJ, Blair SN, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the

American Heart Association. Med Sci Sports Exerc. 2007;39(8):1435-1445. doi: 10.1249/mss.0b013e3180616aa2.

38. Umpierre D, Ribeiro PA, Kramer CK, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes a systematic

review and meta-analysis. JAMA. 2011;305(17):1790-1799. doi: 10.1001/jama.2011.576.

39. Kodama S, Tanaka S, Heianza Y, et al. Association between physical activity and risk of all-cause mortality and cardiovascular disease in patients with diabetes: a metaanalysis.

Diabetes Care. 2013;36(2):471-479. doi: 10.2337/dc12-0783.

40. Colberg SR, Sigal RJ, Yardley JE, et al. Physical activity/exercise and diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2016;39(11):2065-

2079. doi: 10.2337/dc16-1728.

Cardiovascular Health

41. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580-591. doi:

10.1056/NEJMoa0706245.

42. Skyler JS, Bergenstal R, Bonow RO, et al; American Diabetes Association; American College of Cardiology Foundation; American Heart Association. Intensive glycemic

control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association

and a scientific statement of the American College of Cardiology Foundation and the American Heart Association [published correction appears in Diabetes Care.

2009;32(4):754]. Diabetes Care. 2009;32(1):187-192. doi: 10.2337/dc08-9026.

43. Duckworth W, Abraira C, Moritz T, et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes [published correction appears

in N Engl J Med. 2009;361(10):1028; N Engl J Med. 2009;360(10):1024-1025]. N Engl J Med. 2009;360(2):129-139. doi: 10.1056/NEJMoa0808431.

44. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-1589.

doi: 10.1056/NEJMoa0806470.

45. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular

events in type 2 diabetes: meta-analysis of randomized controlled trials. BMJ. 2011;343:d4169. doi: 10.1136/bmj.d4169.

46. Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in U.S. diabetes care, 1999-2010. N Engl J Med. 2013;368(17):1613-1624. doi:

10.1056/NEJMsa1213829.

47. Gregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014;370(16):1514-1523. doi: 10.1056/

NEJMoa1310799.

48. Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Intensive diabetes

treatment and cardiovascular outcomes in type 1 diabetes: the DCCT/EDIC study 30-year follow-up. Diabetes Care. 2016;39(5):686-693. doi: 10.2337/dc15-1990.

Aspirin

49. Antithrombotic Trialists’ (ATT) Collaboration; Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative

meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9676):1849-1860. doi: 10.1016/S0140-6736(09)60503-1.

50. Belch J, MacCuish A, Campbell I, et al; Prevention of Progression of Arterial Disease. and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians

Edinburgh. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomized placebo controlled trial of aspirin and antioxidants

in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840. doi: 10.1136/bmj.a1840.

51. De Berardis G, Sacco M, Strippoli GF, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled

trials. BMJ. 2009;339:b4531. doi: 10.1136/bmj.b4531.

52. Pignone M, Alberts MJ, Colwell JA, et al; American Diabetes Association; American Heart Association; American College of Cardiology Foundation. Aspirin for primary

prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart

Association, and an expert consensus document of the American College of Cardiology Foundation [published corrections appear in Diabetes Care. 2011;34(1):247-248;

Diabetes Care. 2010;33(9):2129-2131]. Diabetes Care. 2010;33(6):1395-1402. doi:10.2337/dc10-0555.

53. Mora S, Manson JE. Aspirin for primary prevention of atherosclerotic cardiovascular disease advances in diagnosis and treatment. JAMA Intern Med. 2016;176(8):1195-

1204. doi: 10.1001/jamainternmed.2016.2648.

Stress Testing

54. Young LH, Wackers FJ, Chyun DA, et al; DIAD Investigators. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes:

the DIAD study: a randomized controlled trial. JAMA. 2009;301(15):1547-1555. doi:10.1001/jama.2009.476.

55. Bax JJ, Young LH, Frye RL, Bonow RO, Steinberg HO, Barrett EJ; ADA [American Diabetes Association]. Screening for coronary artery disease in patients with diabetes.

Diabetes Care. 2007;30(10):2729-2736. doi: 10.2337/dc07-9927.

56. Gibbons RJ, Balady GJ, Bricker JT; et al. ACC/AHA 2002 guideline update for exercise testing: a report of the American College of Cardiology/American Heart Association

task force on Practice Guidelines (Committee on Exercise Testing) 2002. American College of Cardiology website. doi.org/10.1016/S0735-1097(02)02164-2.

57. Budoff MJ, Achenbach S, Blumenthal RS, et al; American Heart Association Committee on Cardiovascular Imaging and Intervention; American Heart Association Council

on Cardiovascular Radiology and Intervention; American Heart Association Committee on Cardiac Imaging, Council on Clinical Cardiology. Assessment of coronary artery

disease by cardiac computed tomography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council

on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation. 2006;114(16):1761-1791.

Lipids

58. Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications

of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines [published correction appears in Circulation. 2004;110(6):763].

Circulation. 2004;110(2):227-239. doi: 10.1161/01.CIR.0000133317.49796.0E.

59. Cholesterol Treatment Trialists’ (CTT) Collaborators; Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14

randomized trials of statins: a meta-analysis. Lancet. 2008;371(9607):117-125. doi: 10.1016/S0140-6736(08)60104-X.

60. Colhoun HM, Betteridge DJ, Durrington PN, et al; CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the

Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685-696. doi: 10.1016/S0140-6736(04)16895-5.

61. ACCORD Study Group; Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus [published correction appears

in N Engl J Med. 2010;362(18):1748]. N Engl J Med. 2010;362(17):1563-1574. doi:10.1056/NEJMoa1001282.

62. Liu J, Sempos CT, Donahue RP, Dorn J, Trevisan M, Grundy SM. Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive

values in coronary heart disease. Am J Cardiol. 2006;98(10):1363-1368. doi: 10.1016/j.amjcard.2006.06.032.

63. Bays HE, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert

Rev Cardiovasc Ther. 2008;6(3):391-409. doi: 10.1586/14779072.6.3.391.

64. Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. 2008;83(4):470-478. doi: 10.4065/83.4.470.

65. Davidson MH. The use of colesevelam hydrochloride in the treatment of dyslipidemia: a review. Expert Opin Pharmacother. 2007;8(15):2569-2578. doi:

10.1517/14656566.8.15.2569.

66. Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J

Med. 2008;359(21):2195-2207. doi: 10.1056/NEJMoa0807646.

67. Ganda OP. Dyslipidemia: pathogenesis and management. In: Poretsky L, ed. Principles of Diabetes Mellitus. 2nd ed. New York, NY: Springer; 2010:435-456.

68. Boden WE, Probstfield JL, Anderson T, et al; AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J

Med. 2011;365(24):2255-2267. doi: 10.1056/NEJMoa1107579.

69. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375(9716):735-742. doi:

10.1016/S0140-6736(09)61965-6.

70. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline

on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association

Task Force on Practice Guidelines [published corrections appear in J Am Coll Cardiol. 2015;66(24):2812. J Am Coll Cardiol. 2014;63(25 Pt B):3024-3025]. J Am Coll Cardiol.

2014;63(25 Pt B):2889-2934. doi: 10.1016/j.jacc.2013.11.002.

71. Cannon CP, Blazing MA, Giugliano RP, et al; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387-2397. doi: 10.1056/NEJMoa1410489.

72. Sabatine MS, Giugliano RP, Keech AC, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N

Engl J Med. 2017;376(18):1713-1722. doi: 10.1056/NEJMoa1615664.

73. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 Focused Update of the 2016 ACC Expert consensus decision pathway on the role of non-statin therapies for LDL cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2017;70(14):1785-1822.

Blood Pressure

74. Stamler J, Vaccaro O, Neaton JD, Wentworth D; Multiple Risk Factor Intervention Trial Research Group. Diabetes, other risk factors, and 12-year cardiovascular mortality

for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16(2):434-444. doi: 10.2337/diacare.16.2.434.

75. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. [published

correction appears in BMJ. 1999;318(7175):29]. BMJ. 1998;317(7160):703-713 . doi:10.1136/bmj.317.7160.703.

76. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results

of the HOPE study and MICRO-HOPE substudy [published correction appears in Lancet. 2000;356(9232):860]. Lancet. 2000;355(9200):253-259.

77. Bibbins-Domingo K, Chertow GM, Coxson PG, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010;362(7):590-599. doi:

10.1056/NEJMoa0907355.

78. Whelton PK, Barzilay J, Cushman WC, et al; ALLHAT Collaborative Research Group. Clinical outcomes in antihypertensive treatment of type 2 diabetes, impaired

fasting glucose concentration, and normoglycemia: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med.

2005;165(12):1401-1409. doi: 10.1001/archinte.165.12.1401.

79. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of

expectations from prospective epidemiological studies. BMJ. 2009;338:b1665. doi:10.1136/bmj.b1665.

80. Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359(15):1565-

1576. doi: 10.1056/NEJMoa0806359.

81. ACCORD Study Group; Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med.

2010;362(17):1575-1585. doi: 10.1056/NEJMoa1001286.

82. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of high blood pressure, 1998-2008. JAMA. 2010;303(20):2043-2050. doi:

10.1001/jama.2010.650.

83. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed

to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. doi: 10.1001/jama.2013.284427.

84. Wright JT Jr, Fine LJ, Lackland DT, Ogededbe G, Dennison Himmelfarb CR. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged

60 years or older: the minority view. Ann Intern Med. 2014;160(7):499-503. doi:10.7326/M13-2981.

85. Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2015;313(6):603-615.

doi: 10.1001/jama.2014.18574.

86. Brunström M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses.

BMJ. 2016;352:i717. doi: 10.1136/bmj.i717.

87. Whelton PK, Carey RM. The 2017 American College of Cardiology/American Heart Association Clinical Practice Guideline for High Blood Pressure in Adults. JAMA

Cardiol 2018;3(4):352-353.

Renal

88. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 [published

correction appears in BMJ. 1999;318(7175):29]. BMJ. 1998;317(7160):703-713.

89. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive

treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC)

Study. JAMA. 2003;290(16):2159-2167. doi: 10.1001/jama.290.16.2159.

90. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD; Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med.

1993;329(20):1456-1462. doi: 10.1056/NEJM199311113292004.

91. Brenner BM, Cooper ME, de Zeeuw D, et al; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869. doi:10.1056/NEJMoa011161.

92. Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P; Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The

effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870-878. doi: 10.1056/NEJMoa011489.

93. Seaquest ER, Ibrahim HN. Approach to the patient with type 2 diabetes and progressive kidney disease. J Clin Endocrinol Metab. 2010;95(7):3103-3110. doi:

10.1210/jc.2010-0504.

94. Rosolowski ET, Skupien J, Smiles A, et al. Risk for ESRD in type 1 diabetes remains high despite renoprotection. J Am Soc Nephrol. 2011;22(3):545-553. doi: 10.1681/

ASN.2010040354.

95. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308. doi: 10.1681/

ASN.2012070718.

96. Tonelli M, Wanner C; Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group members. Lipid management in chronic kidney disease:

synopsis of the Kidney Disease: Improving Global Outcomes 2013 clinical practice guideline. Ann Intern Med. 2014;160(3):182-189. doi: 10.7326/M13-2453.

97. American Diabetes Association. Standards of medical care in diabetes—2017. Diabetes Care. 2017;40(suppl 1):S88-S98. doi: 10.2337/dc17-S013.

98. Bangalore S, Fakheri R, Toklu B, Messerli FH. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and metaanalysis

of randomized trials. BMJ. 2016;352:i438. doi: 10.1136/bmj.i438.

Ocular

99. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of

complications in patients with type 2 diabetes (UKPDS 33) [published correction appears in 1998;354(9178):602]. Lancet. 1998;352(9131):837-853.

100. 100. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes:

UKPDS 38 [published correction appears in BMJ. 1999;318(7175):29]. BMJ. 1998;317(7160):703-713.

101. 101. Holman RR, Paul SK, Bethel MA, Matthew DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359((15):1577-1589.

doi: 10.1056/NEJMoa0806470.

102. 102. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group; Lachin JM, Genuth S, Cleary

P, Davis MD, Nathan DM. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy [published correction appears in

N Engl J Med. 2000;342(18):1376]. N Engl J Med. 2000;342(6):381-389. doi: 10.1056/NEJM200005043421820.

103. 103. White NH, Sun W, ClearyPA, et al. Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus:

10 years after the Diabetes Control and Complications Trial. Arch Ophthalmol. 2008;126(12):1707-1715. doi: 10.1001/archopht.126.12.1707.

104. 104. Early Treatment Diabetic Retinopathy Study research group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report

number 1. Arch Ophthalmol. 1985;103(12):17961806.

105. 105. Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology.

1991;98(5 suppl):766785.

106. 106. Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the

modified Airlie House Classification. ETDRS report number 10. Ophthalmology. 1991;98(suppl 5):786806.

107. 107. Elman MJ, Bressler NM, Qin H, et al; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser

or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011;118(4):609-614. doi: 10.1016/j.ophtha.2010.12.033.

108. 108. Chaturvedi N, Porta M, Klein R, et al; DIRECT Programme Study Group. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect

1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet. 2008;72(9647):1394-1402. doi: 10.1016/S0140-6736(08)61412-9.

109. 109. Sjølie AK, Klein R, Porta M, et al; DIRECT Programme Study Group. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECTProtect

2): a randomised placebo-controlled trial. Lancet. 2008;372(9647):1385-1393. doi: 10.1016/S0140-6736(08)61411-7.

110. Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA. 2007;298(8):902-916. doi: 10.1001/jama.298.8.902.

111. Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, et al. Panretinal photocoagulation vs intravitreous ranibizumab

for proliferative diabetic retinopathy: a randomized clinical trial [published correction appears in JAMA. 2015;315(9):944. JAMA. 2015;314(20):2137-2146. doi:

10.1001/jama.2015.15217.

Peripheral Neuropathy

112. Boulton AJ, Vinik AI, Arezzo JC, et al; American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care.

2005;28(4):956-962. doi: 10.2337/diacare.28.4.956.

113. Freeman R. Autonomic peripheral neuropathy. Lancet. 2005;365(9466):1259-1270. doi: 10.1016/S0140-6736(05)74815-7.

114. American Diabetes Association: Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(suppl 1):S11-S63. doi: 10.2337/dc12-s011.

115. Spallone V, Lacerenza M, Rossi A, Sicuteri R, Marchettini P. Painful diabetic polyneuropathy: approach to diagnosis and management. Clin J Pain. 2012;28(8):726-743. doi:

10.1097/AJP.0b013e318243075c.

116. Pop-Busui R, Boulton A, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-154. doi:

10.2337/dc16-2042.

117. Vinik AI. Clinical practice: diabetic sensory and motor neuropathy [published correction appears in N Engl J Med. 2016;374(18):1797; N Engl J Med. 2016;375(14):1402].

N Engl J Med. 2016;374(15):1455-1464. doi: 10.1056/NEJMcp1503948.

Feet

118. American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(suppl 1):S11-S63.

119. Valk GD, Kriegsman DM, Assendelft WJ. Patient education for preventing diabetic foot ulceration. Cochrane Database Syst Rev. 2005;(1):CD001488. doi:

10.1002/14651858.CD001488.pub2.

120. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293(2):217-228. doi: 10.1001/jama.293.2.217.

121. Hingorani A, LaMuraglia GM, Henke P, et al. The management of diabetic foot: a clinical practice guideline by the Society for Vascular Surgery in collaboration with the

American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg. 2016;63(suppl 2):3S-21S. doi: 10.1016/j.jvs.2015.10.003.

Behavioral HealthAdherence

122. Anderson BJ, Vangsness L, Connell A, Butler D, Goebel-Fabbri A, Laffel LM. Family conflict, adherence, and glycemic control in youth with short duration type 1

diabetes. Diabet Med. 2002;19(8):635-642.

123. Odegard PS, Capoccia K. Medication taking and diabetes: a systematic review of the literature. Diabetes Educ. 2007;33(6):1014-1029; discussion 1030-1031. doi:

10.1177/0145721707308407.

124. Skovlund SE, Peyrot M. The Diabetes Attitudes, Wishes, and Needs (DAWN) program: a new approach to improving outcomes of diabetes care. Diabetes Spectrum. 2005;18(3):136-142.

Anxiety

125. Grigsby AB, Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. Prevalence of anxiety in adults with diabetes: a systematic review. J Psychosom Res. 2002;53(6):1053-1060.

Depression

126. Anderson R, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001;24(6):1069-

1078. doi: 10.2337/diacare.24.6.1069.

127. de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depression and diabetes complications: a meta-analysis. Psychosom Med.

2001;63(4):619-630.

128. Gonzalez JS, Safre SA, Cagliero E, et al. Depression, self-care, and medication adherence in type 2 diabetes: relationships across the full range of symptom severity.

Diabetes Care. 2007;30(9):2222-2227. doi: 10.2337/dc07-0158.

129. Grey M, Whittemore R, Tamborlane W. Depression in type 1 diabetes in children: natural history and correlates. J Psychosom Res. 2002;53(4):907-911. doi: 10.1016/

S0022-3999(02)00312-4.

130. Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care. 2000;23(7):934-942.

131. Talbot F, Nouwen A. A review of the relationship between depression and diabetes in adults: is there a link? Diabetes Care. 2000;23(10):1556-1562.

Eating Disorders

132. Goebel-Fabbri AE, Fikkan J, Franko DL, Pearson K, Anderson BJ, Weinger K. Insulin restriction and associated morbidity and mortality in women with type 1 diabetes.

Diabetes Care. 2008;31(3):415-419. doi: 10.2337/dc07-2026.

Immunizations

133. Smith SA, Poland GA. Use of influenza and pneumococcal vaccines in people with diabetes. Diabetes Care. 2000;23(1):95-108.

134. tps://l care in diabetes ng an overall list for Front matter iwth ized controlled trials. Acta Diabetol. 2018;55(5):429-r

135. American Diabetes Association. Standards of medical care in diabetes 2017. Diabetes Care. 2017;40(suppl 1):S25-S32. doi: 10.2337/dc17-S006. Women’s Health

136. Holing EV. Preconception care of women with diabetes: the unrevealed obstacles. J Matern Fetal Med. 2000;9(1):10-13.

137. Schwartz AV, Sellmeyer DE. Women, type 2 diabetes, and fracture risk. Curr Diab Rep. 2004;4(5):364-369.

138. Enzlin P, Mathieu C, Van den Bruel A, Bosteels J, Vanderschueren D, Demyttenaere K. Sexual dysfunction in women with type 1 diabetes: a controlled study. Diabetes Care.

2002;25(4):672-677. doi: 10.2337/diacare.25.4.672.

139. Nicodimus KK, Folsom AR; Iowa Women’s Health Study. Type 1 and type 2 diabetes and incidence of hip fractures in postmenopausal women. Diabetes Care.

2001;24(7):1192-1197.

140. Holmberg AH, Nilsson PM, Nilsson JA, Akesson K. The association between hyperglycemia and fracture risk in middle age. a prospective, population-based study

of 22,444 men and 10,902 women. J Clin Endocrinol Metab. 2008;93(3):815-822. doi:10.1210/jc.2007-0843.

Women’s Health

136. Holing EV. Preconception care of women with diabetes: the unrevealed obstacles. J Matern Fetal Med. 2000;9(1):10-13.

137. Schwartz AV, Sellmeyer DE. Women, type 2 diabetes, and fracture risk. Curr Diab Rep.2004;4(5):364-369.

138. Enzlin P, Mathieu C, Van den Bruel A, Bosteels J, Vanderschueren D, Demyttenaere K. Sexual dysfunction in women with type 1 diabetes: a controlled study. Diabetes Care.

2002;25(4):672-677. doi: 10.2337/diacare.25.4.672.

139. Nicodimus KK, Folsom AR; Iowa Women’s Health Study. Type 1 and type 2 diabetes and incidence of hip fractures in postmenopausal women. Diabetes Care.

2001;24(7):1192-1197.

140. Holmberg AH, Nilsson PM, Nilsson JA, Akesson K. The association between hyperglycemia and fracture risk in middle age. a prospective, population-based study

of 22,444 men and 10,902 women. J Clin Endocrinol Metab. 2008;93(3):815-822. doi:10.1210/jc.2007-0843.

Men’s Health

141. Lue TF. Erectile dysfunction. N Engl J Med. 2000;342(24):1802-1813. doi: 10.1056/NEJM200006153422407.

142. Beckman TJ, Abu-Lebdeh HS, Mynderse LA. Evaluation and medical management of erectile dysfunction. Mayo Clin Proc. 2006;81(3):385-390. doi:

10.4065/81.3.385.

143. Nehra A. Erectile dysfunction and cardiovascular disease: efficacy and safety of phosphodiesterase type 5 inhibitors in men with both conditions. Mayo Clin Proc.

2009;84(2):139-148. doi: 10.1016/S0025-6196(11)60822-7.

Dental Care

144. Simpson TC, Needleman I, Wild SH, Moles DR, Mills EJ. Treatment of periodontal disease for glycaemic control in people with diabetes. Cochrane Database Syst Rev.

2010;(5):CD004714. doi: 10.1002/14651858.CD004714.pub2.

145. Bahekar AA, Singh S, Saha S, Molnar J, Arora R. The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis. Am

Heart J. 2007;154(5):830-837. doi: 10.1016/j.ahj.2007.06.037.

146. Humphrey LL, Fu R, Buckley DI, Freeman M, Helfand M. Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis. J Gen Intern

Med. 2008;23(12):2079-2086. doi: 10.1007/s11606-008-0787-6.

Sleep Apnea

147. Foster GD, Borradaile KE, Sanders MH, et al; Sleep AHEAD Research Group of Look AHEAD Research Group. A randomized study on the effect of weight loss on obstructive

sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD study. Arch Intern Med. 2009;169(17):1619-1626. doi: 10.1001/archinternmed.2009.266.

148. Jordan AS, McSharry D, Malhotra A. Adult obstructive sleep apnea. Lancet. 2014;383(9918):736-747. doi: 10.1016/S0140-6736(13)60734-5.

149. McEvoy RD, Antic NA, Heeley E, et al; SAVE Investigators and Coordinators. CPAP

for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375(10):919-931. doi: 10.1056/NEJMoa1606599.

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