Resident Editors: Scott Goldberg, MD, Katherine Wysham, MD
Faculty Editor: Alka Kanaya, MD
BOTTOM LINE ✔ T2DM is insulin resistance and relative insulin deficiency ✔ A1c ≥6.5% and/or fasting glucose ≥126 mg/dl are two diagnostic criteria ✔ New guidelines emphasize the role of CV risk reduction |
Background
- Diabetes mellitus (DM) affects >9.3% of the population (as of 2012) and is a leading cause of coronary artery disease, blindness, peripheral vascular disease, and renal failure
- ASCVD – defined as coronary heart disease, cerebrovascular disease, or peripheral arterial disease – is the leading cause of morbidity and mortality for individuals with DM and is the largest contributor to the direct and indirect costs of diabetes
- Etiology is thought to be insulin resistance combined with relative insulin deficiency
- Appropriate management requires a comprehensive, multidisciplinary approach
- The American Diabetes Association 2018 guidelines emphasize the role of ASCVD risk reduction in the care of patients with DM
- The American Academy of Endicronologists (AACE) has a helpful and comprehensive mobile app for diabetes care
Signs and Symptoms
- Signs: Obesity, acanthosis nigricans, central adiposity
- Symptoms: Weight gain, polyuria, polydipsia, blurred vision, vulvovaginitis, peripheral neuropathy, gastroparesis, or asymptomatic
Screening
USPSTF:
- Screen for abnormal glucose as part of CV risk assessment in adults aged 40-70 years who are overweight or obese (Grade B recommendation)
- Persons who have a family history of DM, have a history of gestational DM or PCOS, or are members of certain racial/ethnic groups (African Americans, American Indians, or Alaskan Natives, Asian Americans, Hispanics or Latinos, or Native Hawaiians or Pacific Islanders) may be at increased risk of DM at a younger age or at a lower BMI
- Consider screening earlier in persons with 1 or more of these characteristics
- Re-screening every 3 years may be a reasonable approach for adults with normal blood glucose levels
ADA:
Testing should be considered in overweight (BMI >25 or >23 kg/m2 in Asian Americans) adults who have one or more of the following risk factors:
- First-degree relative with DM
- High-risk race/ethnicity
- History of CVD
- Hypertension
- HDL <35 and/or Total cholesterol >250 mg/dl
- PCOS
- Physical inactivity
- Other conditions associated with insulin resistance (Severe obesity, acanthosis nigricans)
- Patients with pre-diabetes (A1c 5.7 – 6.4%)
- Women who were diagnosed with GDM should get tested every 3 years
- For all other patients, testing should begin at age 45.
Diagnostic Criteria: (a positive test result for diabetes should be confirmed by repeat testing)
|
Prediabetes |
Diabetes |
---|---|---|
HbA1c* |
5.7-6.4% |
≥6.5% |
Fasting plasma glucose |
100-125 mg/dL |
≥126 mg/dL |
Oral glucose tolerance test |
140-199 mg/dL |
≥200 mg/dL |
Random plasma glucose |
|
≥200 mg/dL |
*Hemoglobin A1c: Not dependable in disorders of hemoglobin such as pregnancy, post-transfusion, hemoglobinopathies including sickle cell disease and trait.
Pre-Diabetes:
- Should not be viewed as a clinical entity in its own right but rather as an increased risk for DM and CVD
- Follow closely and repeat screening for pre-DM in 3-6 months
- People with pre-DM should be referred to an intensive behavioral lifestyle intervention program modeled on the Diabetes Prevention Program to achieve and maintain 7% loss of initial body weight and increase moderate-intensity physical activity to at least 150 min/week
- Metformin therapy can be considered for prevention of DM in people with pre-DM who have severe obesity, young age, and women with prior GDM
History and Physical
- Past Medical History:
- Diabetes history
- Age and symptoms at onset
- Past hospitalizations
- Prior treatment regimens
- Personal history of complications and common comorbidities
- Macrovascular and microvascular
- Hypertension, hyperlipidemia
- Dental care
- Vaccination history
- Psychosocial conditions (depression, anxiety)
- Diabetes history
- Social History:
- Lifestyle (diet, activity, sleep)
- Housing
- Tobacco, alcohol, and substance use
- Social supports
- Family History:
- History of DM in first-degree relative
- History of autoimmune disease
- Physical Exam:
- Vitals, BMI
- Skin (e.g. acanthosis nigricans)
- Foot (visual inspection, pulses, vibration or pinprick, monofilament)
- Labs:
- A1c, fasting lipid profile, BMP, LFTs, spot urinary alb/cr ratio
Lifestyle Management
- Self-Management Education
- All people with DM should participate in diabetes self-management education to facilitate the knowledge, skills, and ability necessary for diabetes self-care
- Effective education should be patient-centered and may be given in group or individual settings, and use technology when appropriate
- Nutrition
- Goals of nutrition therapy are to promote and support healthful eating patterns in achieving and maintaining body weight, glycemic, BP, and lipid goals while addressing individual and cultural preferences
- The diabetes plate method is a simple guide for planning meals – fill ½ the plate with non-starchy vegetables, ¼ with whole grain foods or starchy vegetables, and the remaining ¼ with lean protein
- Weight Management
- Strong evidence that modest persistent weight loss can delay the progression from pre-DM to DM and is beneficial to the management of DM
- Alcohol
- Moderate EtOH does not have major detrimental effects on long-term blood glucose control
- Risks associated with excessive use include hypoglycemia or hyperglycemia and weight gain
- Physical Activity
- 150 min or more of moderate-to-vigorous intensity aerobic activity per week, spread over at least 3 days/week, with no more than 2 consecutive days without activity
- Reduce amount of time spent in daily sedentary behavior
- Psychosocial Issues
- Diabetes care should be collaborative, patient-centered
- Screen for attitudes about DM, expectations, patient goals, mood, quality of life, financial resources, cognitive impairment (in the elderly)
Pharmacotherapy
- Primary goal: A1c <7%. May intensify goal to <6.5% for patients with easily managed diabetes if it can be obtained without frequent lows. May relax goal to <8% for elderly, those who experience frequent lows or for those who already have severe micro/macrovascular disease.
- Secondary goals: FBG 70-130 mg/dl; 2-hr postprandial glucose <180 mg/dl.
- Perform A1c at least two times a year in patients who are meeting treatment goals and quarterly in those who are not
- Point-of-care testing for A1c allows for more timely treatment changes
Approach to Pharmacotherapy
- Medication should always be in addition to lifestyle management
- Metformin, if not contraindicated and if tolerated, is the preferred initial pharmacologic agent
- Consider initiating insulin therapy in patients with newly diagnosed DM2 who are symptomatic and/or have A1c ≥ 10% and/or BG ≥ 300 mg/dL
- If A1c…
- <9% → consider monotherapy with metformin
- If A1c not at target in 3-4 months, then consider dual therapy.
- ≥9% → dual therapy with metformin + additional agent
- ASCVD?
- Yes → add agent proven to reduce major adverse CV events and/or CV mortality (liraglutide/empaglifozin then canaglifozin)
- No → add second agent based on drug-specific effects and patient factors (see table below)
- If A1c not at goal after 3-4 months on dual therapy, ask about medication adherence and consider triple therapy (metformin + non-insulin agent + insulin)
- ASCVD?
- If A1c >10% or target not achieved with two agents, start basal insulin
- If A1c not controlled, consider combination injectable therapy with either of these 3 options:
- Add 1 rapid-acting insulin before largest meal
- If A1c target not achieved, advance to basal-bolus
- Add GLP-1 receptor agonist
- If A1c target not achieved or not tolerated, change to 2 insulin regimen (basal-bolus)
- Change to premixed insulin twice daily (before breakfast and dinner)
- If A1c target not achieved, change to premixed analog insulin 3 times daily
- Add 1 rapid-acting insulin before largest meal
- If A1c not controlled, consider combination injectable therapy with either of these 3 options:
- <9% → consider monotherapy with metformin
Non-Insulin Therapies to Combine with Metformin
|
Sulfonylureas (2ndgeneration) |
TZDs |
SGLT2 inhibitors |
DPP-4 inhibitors |
GLP-1 receptor agonists (injectable) |
---|---|---|---|---|---|
Medications in this class |
Glipizide, glyburide |
Pio-, rosiglitazone |
Cana-, empaglifozin |
Sita-, saxa-, linagliptin |
Liraglutide (qd), Exenatide ER (qwk), dulaglutide (qwk), albiglutide (qwk) |
A1c reduction |
1.25 |
1 |
0.6-0.8 |
0.5-0.8 |
1 |
Hypoglycemia |
Yes |
No |
No |
No |
No |
Weight |
Gain |
Gain |
Loss |
Neutral |
Loss |
Side effects |
First-generation may have increased risk for CV mortality |
May cause fluid retention and worsen CHF |
Risk of amputation (canaglifozin), DKA, GU infections |
Risk of CHF with saxa- and alogliptin |
GI side effects, risk of thyroid C-cell tumors |
ASCVD Profile |
Neutral |
Potential benefit w/ pioglitazone |
Benefit w/ canaglifozin and empaglifozin |
Neutral |
Benefit with liraglutide |
Cost |
Low |
Low |
High |
High |
High |
Types of Insulin
- Patients with DM2 generally require 0.7-1.0 u/kg/day
- Decision to begin insulin should be individualized
- Choice of insulin based on individual patient factors and availability, but basal insulin is preferred
Action type |
Example |
Onset |
Peak |
Duration |
---|---|---|---|---|
Ultra-short |
lispro, aspart, or glulisine |
<15 min |
1-2 hr |
<6 hr |
Short |
regular |
0.5-1 hr |
2-4 hr |
5-8 hr |
Intermediate |
NPH |
1-2 hr |
6-10 hr |
12+ hr |
Long |
glargine or detemir |
1-1.5 hr |
None |
12-24 hr |
Step 1: Start bedtime basal insulin.
- Start 10U/day or 0.1-0.2U/kg/day
- Adjust 10-15% or 2-4U once or twice weekly to reach FBG target (90-130 mg/dL)
- If hypoglycemia occurs, decrease dose by ≥ 4units or by 10% if dose >60 units
Step 2: Additional injection (if A1c ≥7% despite FBG in target range 90-130 or >0.5u/kg basal insulin)
- Change to premixed insulin twice daily (before breakfast and dinner)
- Divide current basal dose into 2/3 AM and 1/3 PM or ½ AM and ½ PM
- Adjust dose by 1-2U or 10-15% once or twice weekly until target BG reached
- Change to rapid-acting insulin before largest meal
- Start with 4U, 0.1U/kg, or 10% basal dose
- Increase dose by 1-2U or 10-15% once or twice weekly until target BG reached
- If A1c not controlled, add >2 rapid-acting insulin injections before each meals (“basal-bolus”)
Management of Macrovascular and Microvascular Complications
ASCVD – defined as coronary heart disease, cerebrovascular disease, or peripheral arterial disease – is the leading cause of morbidity and mortality for individuals with DM and is the largest contributor to the direct and indirect costs of diabetes. Therefore, CV risk factors should be systematically assessed at least annually in all patients.
GLYCEMIC CONTROL |
||
---|---|---|
A1c |
Q3 months |
Goal <7% Check Q6 months when stable |
MICRO AND MACROVASCULAR COMPLICATIONS |
||
Blood Pressure |
Each visit |
|
Lipid Control |
Annually |
|
Aspirin |
Each visit |
|
Dilated Eye Exam |
Annually |
|
Foot Exam
|
Annually
|
|
Diabetic Kidney Disease |
Annually |
|
OTHER HEALTH CARE MAINTENANCE |
||
Influenza Vaccine |
Annually |
|
Pneumococcal Vaccine |
Once |
Repeat x1 if first vaccine was given before age 65 and >5 years ago |
Dental Care |
Annually |
|
Smoking Cessation |
Each Visit |
For smokers only |
Education & Self-management Review |
Annually |
|
References
Association, American Diabetes. “Professional Practice Committee: Standards of Medical Care in Diabetes—2018.” Diabetes Care 41, no. Supplement 1 (January 1, 2018): S3–S3.
Henske JA, Griffith ML and Fowler MJ. “Initiating and Titrating Insulin in Patients With Type 2 Diabetes.” Clinical Diabetes 2009;27(2):72-76
Lipska KJ, Bailey CJ and Inzucchi SE. “Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency.” Diabetes Care 2011;34(6):1431-1437
Nathan, DM et al. “Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy.” Diabetes Care 2009;32(1):193-203.
Palmer, Suetonia C., Dimitris Mavridis, Antonio Nicolucci, David W. Johnson, Marcello Tonelli, Jonathan C. Craig, Jasjot Maggo, et al. “Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis.” JAMA 316, no. 3 (July 19, 2016): 313–24.