Prediabetes and Diabetes Type 2: Screening and Making the Diagnosis
Clinical Actions:
Diabetes results when the pancreas cannot respond to or produce insulin, leading to abnormal metabolism of carbohydrates and elevated levels of glucose in the blood and urine. Type 2 diabetes (previously “noninsulin-dependent diabetes” or “adult-onset diabetes”) accounts for 90–95% of all diabetes. Type 2 diabetes is caused by a progressive loss of β-cell insulin secretion, usually associated with insulin resistance. Prediabetes is diagnosed when glucose levels start to rise due to β-cell insulin secretion failure, but diagnostic criteria are not yet met for Type 2 diabetes.
Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
People with HIV
Screen for diabetes and prediabetes with a fasting glucose test
Before starting antiretroviral therapy
At the time of switching antiretroviral therapy
3 to 6 months after starting or switching antiretroviral therapy
If initial screening results are normal, fasting glucose should be checked annually
Patients with prediabetes (A1C ≥5.7% [39 mmol/mol], IGT, or IFG) should be tested yearly
Women who were diagnosed with GDM should have lifelong testing at least every 3 years
For all other patients, testing should begin at age 35 years
If results are normal, testing should be repeated at a minimum of 3-year intervals, with consideration of more frequent testing depending on initial results and risk status
AACE/ACE
Begin at age 45 without risk factors
Screening based on risk factors: In addition to the above list, AACE/ACE includes the following factors
Antipsychotic therapy for schizophrenia and/or severe bipolar disease
Chronic glucocorticoid exposure
Sleep disorders (e.g., obstructive sleep apnea, chronic sleep deprivation, and night shift occupation) with glucose intolerance
Normal glucose values: Every 3 years
Consider annual screening for patients with 2 or more risk factors
USPSTF
Screen for prediabetes and type 2 diabetes in adults aged 35 to 70 years who have overweight (BMI ≥25) or obesity (BMI ≥30)
Clinicians should offer or refer patients with prediabetes to effective preventive interventions
Above are Grade B recommendations: Offer or provide this service
Diagnostic Criteria
Normal
Fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol per L)
Oral glucose tolerance test (OGTT) with 75g glucose load
2h (plasma glucose) PG <140 mg/dL (7.8 mmol per L)
High Risk for Diabetes (prediabetes)
Impaired fasting glucose (IFG): FPG ≥100 to 125 mg/dL (5.6 to 6.9 mmol per L)
Impaired glucose tolerance (IGT): 2h PG ≥140 to 199 mg/dL (7.8 to 11.0 mmol per L)
A1C 5.7% to 6.4%
Note: Patients with prediabetes should be tested yearly
Diabetes: Glucose criteria are preferred for the diagnosis of DM
FPG ≥126 (7.0 mmol per L) mg/dL
OGTT: 2h PG ≥200 mg/dL (11.1 mmol per L)
Random PG ≥200 mg/dL (11.1 mmol per L) with the following symptoms of hyperglycemia
Note: Always confirm diabetes diagnosis with repeat glucose or A1C testing on another day
SYNOPSIS:
Prediabetes is not a clinical disorder but rather an important risk factor for diabetes and cardiovascular disease. While there are some differences between organizations regarding risk factors for screening and diagnostic cut-offs, all agree as to the importance of identifying those at risk for significant cardiovascular events if diabetes is left untreated. The prognosis for type 2 diabetes varies and is very dependent on glucose control.
KEY POINTS:
Symptoms of
Diabetes (related to hyperglycemia)
Excessive urination, thirst and hunger
Unexpected weight loss
Increased susceptibility to infections, especially yeast or fungal infections
Weak, tired feeling
Dry mouth
Blurry vision
Deposits of blood, or puffy yellow spots in the retina
Treatment of Type 2 Diabetes, whether new onset or persistent, requires multimodal, comprehensive management. Diabetic treatment includes lifestyle changes, weight management, and pharmacologic approaches. Aside from antihyperglycemic agents, patients may also require lipid-lowering and antihypertensive medications
Initial therapy and A1C
Lifestyle therapy plus antihyperglycemic monotherapy (preferably with metformin)
A1C target (See ‘Related ObG Topic’ below): Currently, there are different professional guideline thresholds
ACP: Aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes and consider deintensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%
ADA: Recommends <7% for the general population and to consider more stringent goals (<6.5%) for selected patients without significant hypoglycemia (e.g., long life expectancy, no CVD and treated with lifestyle or metformin only)
AACE/ACE: ≤6.5% if target can be achieved safely
ADA Treatment Recommendations Include the Following
Metformin is the preferred initial medication if tolerated by patient, with other agents added to metformin as needed to achieve target
Benefits: Low hypoglycemia risk | May help with modest weight loss | Good antihyperglycemic efficacy at doses of 1,000 to 2,000 mg/day
Side effects: GI intolerance (bloating, abdominal discomfort, and diarrhea)
Renal disease: Can be used with reduced estimated glomerular filtration rates (eGFR) ≥30 mL/min/1.73 m2
Vitamin B12 deficiency: Periodically test for vitamin B12 levels
Consider early introduction of insulin
Catabolism: Weight loss | Hypertriglyceridemia | Ketosis
Dual therapy: Consider in newly diagnosed patients if A1C ≥1.5% (12.5 mmol/mol) above target
Initial dual therapy extends time to treatment failure (compared to sequential addition of medications)
High costs and tolerability issues are important barriers to the use of GLP-1 receptor agonists
Continue metformin for as long as tolerated and not contraindicated
Add other agents, including insulin, to metformin
Glucagon-like peptide 1 receptor agonist is preferred to insulin when possible
With Comorbidities in addition to Type 2 Diabetes
In patients with known atherosclerotic cardiovascular disease or at high risk, kidney disease, or heart failure, the following are recommended
Sodium–glucose cotransporter 2 inhibitors
Glucagon-like peptide 1 receptor agonists with demonstrated CVD benefit
Consideration of these medications in the setting of these co-morbidities is independent of HbA1C or HbA1C target
SYNOPSIS:
Management should be individualized based on numerous factors, such as age, life expectancy, comorbid conditions, duration of diabetes, risk of hypoglycemia or adverse consequences from hypoglycemia, patient motivation, and adherence. The ADA states that
A patient-centered approach should be used to guide the choice of pharmacologic agents. Considerations include comorbidities (atherosclerotic cardiovascular disease, heart failure, chronic kidney disease), hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences.
KEY POINTS
Lifestyle Modification
ACCE/ACE list the following as key areas for lifestyle modification
Nutrition: Weight management | plant-based diet
Physical Activity: 150 min/week exertion such as walking or stair climbing | Strength training
Sleep: About 6 to 8 hours/night
Behavioral support: Community engagement | Alcohol moderation
Smoking cessation: No tobacco products
Medications
Noninsulin Glucose-Lowering Agents
Biguanides
Metformin is considered first line medication
Acceptable alternatives (described below) to metformin as initial therapy include
Caution recommended due to associated risk factors: Weight gain | Increased bone fracture risk in postmenopausal females and elderly males | Elevated risk for chronic edema or heart failure
Note: While the ACE/ACCE algorithm (see below in ‘Learn More – Primary Sources) places GLP-RA and SGLT2i drugs as next in line to combine with metformin, the ADA states
If the A1C target is not achieved after approximately 3 months, metformin can be combined with any one of the preferred six treatment options: sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 RA, or basal insulin; the choice of which agent to add is based on drug-specific effects and patient factors
Insulin
Most potent antihyperglycemic agent
Considerations prior to use
Patient motivation | CVD, comorbidities and complications | Age | Risk for Hypoglycemia | Overall health |Cost considerations
Basal analogs: Glargine | Detemir | Degludec
Flat serum insulin concentration for 24 hours or longer
Human Neutral protamine Hagedorn (NPH) insulin
More likely to cause hypoglycemia than basal analogs
Addition of human NPH or long-acting insulin analogs to oral agents is “well-established approach that is effective for many patients” (ADA)
Tremors or feeling shaky | Nervous or anxious | Sweating, chills and clamminess | Irritability | Confusion | Tachycardia | Lightheaded or dizziness | Pallor | Drowsy or weakness | Blurred/impaired vision | Tingling or numbness in the lips, tongue, or cheeks | Headaches | Lack of coordination | Seizures (severe)
“15-15 Rule”: Raise glucose to >70 mg/dL with 15 grams carbohydrate intake and check glucose at 15 minutes | Repeat if glucose still
Glucose tablets or gel tube | 4 ounces (1/2 cup) of juice or regular (non-diet) soda | 1 tablespoon of sugar, honey, or corn syrup | Hard candies, jellybeans, or gumdrops (based on labelling)
Severe hypoglycemia (patient cannot treat herself or unconscious): Glucagon
Available by injection (buttock, arm or thigh) or nasal powder (does not require inhalation)
Additional Notes
GLP1-RA is preferable to insulin for those patients who may require an injectable medication
Patients who require a 3rd medication and who have A1C >8.0% and/or long-standing disease: Less likely to reach their target A1C with a third oral antihyperglycemic agent
While adding GLP1-RA may initially work, many patients will still require insulin
Reevaluate medications regularly
Every 3 to 6 months
Adjust as needed based on new patient factors
Yearly visits (or more frequent depending on clinical findings) to ophthalmologist and podiatrist
Important to prevent complications and slow CVD / renal disease
Manage risk factors for atherosclerosis (e.g., BP, cholesterol, smoking, obesity)
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Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclaimer
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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