Update from the ACP: New Hemoglobin A1c Targets for Type 2 Diabetes Mellitus

SUMMARY:

The ACP has updated guidance to help providers better target hemoglobin A1c (HbA1c) targets for the pharmacologic treatment of type 2 diabetes. The ACP recommends

Clinicians should personalize goals for glycemic control in patients with type 2 diabetes on the basis of a discussion of benefits and harms of pharmacotherapy, patients’ preferences, patients’ general health and life expectancy, treatment burden, and costs of care.

Clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes.

Clinicians should consider deintensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%.

Clinicians should treat patients with type 2 diabetes to minimize symptoms related to hyperglycemia and avoid targeting an HbA1c level in patients with a life expectancy less than 10 years due to advanced age (80 years or older), residence in a nursing home, or chronic conditions (such as dementia, cancer, end-stage kidney disease, or severe chronic obstructive pulmonary disease or congestive heart failure) because the harms outweigh the benefits in this population.

KEY POINTS:  

Other guidelines reviewed in this document include  

  • The ADA guidelines set the following targets  
    • <7% for the general population 
    • Consider less stringent goals (<8%) for patients with limited life expectancy or significant comorbidities
    • Consider more stringent goals (<6.5%) for selected patients without significant hypoglycemia  
      • Short duration of diabetes 
      • Type 2 diabetes treated with lifestyle or metformin only 
      • Long life expectancy 
      • No CVD  

Note: The ADA has issued a statement that it is “deeply concerned by the new guidance” and “that a reasonable A1c goal for many nonpregnant adults with type 2 diabetes is less than 7 percent based on the available evidence to date from the ACCORD, ADVANCE, VADT and UKPDS international clinical trials, which were evaluated and incorporated into ADA’s Standards of Care.” (see ‘Learn More – Primary Sources’ below)

  • Scottish Intercollegiate Guidelines Network (SIGN) guideline is similar to ADA  
  • AACE/ACE  
    • ≤6.5% if target can be achieved safely  
  • NICE  
    • 6.5% for patients managed with 
      • Lifestyle and diet 
      • Lifestyle and diet with single drug and no hypoglycemia 
    • 7% for patients on medications associated with hypoglycemia  
  • Institute for Clinical Systems Improvement  
    • < 7% to < 8% based on patient factors 
  • VA/DoD  
    • 6% to 7% for patients with a life expectancy > 10 to 15 years and no or mild microvascular complications 
    • 7% to 8.5% for those with established microvascular or macrovascular disease, comorbid conditions, or a life expectancy of 5 to 10 years 
    • 8% to 9% for those with a life expectancy <5 years, significant comorbid conditions, advanced complications of diabetes, or difficulties in self-management attributable to mental status, disability, or other factors (12) 

Review of Literature 

Overall, the ACP did not find that the benefits of lower HbA1c targets justified potential risks 

  • ACP reviewed 5 large RCTs comparing intensive (achieved HbA1c levels, 6.3% to 7.4%) versus less intensive (achieved HbA1c levels, 7.3% to 8.4%) treatment targets  
    • Main effect: More intensive glycemic control resulted in small absolute reductions in risk for microvascular surrogate events (e.g., retinopathy on ophthalmologic screening) but not clinical events such as loss of vision  
    • One trial of metformin in overweight adults showed a reduction in all-cause and diabetes-related death through at least 10 years 
    • In all studies, more intensive therapy required higher dose medications and was associated with more adverse events (including increased risk of death in 1 study) 

NOTE: All guidelines allow for higher HbA1c targets depending on comorbid conditions and limited life expectancy 

Learn More – Primary Sources:  

Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians

American Diabetes Association® Deeply Concerned About New Guidance from American College of Physicians Regarding Blood Glucose Targets for People with Type 2 Diabetes

ADA: Glycemic Targets: Standards of Medical Care in Diabetes—2022

American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan – 2022 Update

NICE: Type 2 diabetes in adults: management

VA/DoD Clinical Practice Guidelines: Management of Diabetes Mellitus in Primary Care

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.

Table of Contents  

Evaluate Patients for Risk Factors

Risk Factors for Type 2 Diabetes (NIDDK)

  • Overweight or obese
    • NIDDK BMI chart (see ‘Primary Sources – Learn More’ below)
      • Not Asian American or Pacific Islander: At-risk BMI ≥ 25
      • Asian American: At-risk BMI ≥ 23
      • Pacific Islander: At-risk BMI ≥ 26
  • ≥45 years
  • Family history of diabetes
  • Race/Ethnicity
    • African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander
  • Hypertension (or on therapy for hypertension)
  • Dyslipidemia
  • Personal history of
    • Pregnancy: GDM or macrosomia (BW >4000 g)
    • Physical inactivity
    • Heart disease or stroke
    • Depression
    • PCOS
    • Acanthosis nigricans
    • HIV

Screening and Diagnostic Criteria

Who and When to Screen

ADA

  • Overweight or obesity (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans) and ≥1 of the following risk factors
    • First-degree relative with diabetes
    • High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)
    • History of CVD
    • Hypertension (≥140/90 mmHg or on therapy for hypertension)
    • HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L)
    • Women with polycystic ovary syndrome
    • Physical inactivity
    • 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
      • Polydipsia | Polyuria | Polyphagia | Blurred vision | Weakness | Unexplained weight loss
    • A1C ≥6.5%
    • 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
  • Decreased sensation in the legs
  • Weak pulses in the feet
  • Blisters, ulcers or infections of the feet 

Complications of Type 2 Diabetes

  • Atherosclerosis
  • Retinopathy 
  • Neuropathy 
  • Nephropathy
  • Dermatologic pathology
    • Infections
    • Feet in particular: Ulcerations with poor healing  

Learn More – Primary Sources:

ADA: Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2022

AACE/ACE Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan

Consensus Statement By The American Association Of Clinical Endocrinologists And American College Of Endocrinology On The Comprehensive Type 2 Diabetes Management Algorithm – 2020 Executive Summary

NIDDK: Risk Factors for Type 2 Diabetes

60-Second Type 2 Diabetes Risk Test

USPSTF: Screening for Prediabetes and Type 2 Diabetes

HIV and Diabetes | NIH

ACOG and SMFM Both Release Guidance on Gestational Diabetes – Insulin vs Metformin for First-Line Therapy?

SUMMARY:

The SMFM released a statement on the use of metformin as a first-line alternative to insulin in women with GDM.  ACOG has also released an update to the major 2017 Practice Bulletin which also addresses this issue and still considers insulin the preferred option to treat women who are not adequately controlled with appropriate nutritional therapy.

  • Both the ACOG update and SMFM statement summarize the literature, including recent meta-analyses on the comparison studies between insulin and metformin
    • Data has been conflicting based on whether non-published studies included women with type II diabetes
    • Some studies have demonstrated a higher risk for preterm birth (but lower for gestational hypertension) in the metformin group while other studies have not identified a difference in preterm birth

ACOG

  • Based on current evidence, ACOG states that, consistent with ADA guidance, insulin is the ‘preferred’ approach for GDM for women not sufficiently controlled with diet and exercise
  • In addition, the ACOG update states

Thus, although metformin may be a reasonable alternative approach to treat gestational diabetes, it is important to counsel women about the lack of superiority when compared with insulin, the placental transfer of the drug, and the absence of long-term data in exposed offspring. Additionally, in the aforementioned prospective trials, between 26% and 46% of women who took metformin alone eventually required insulin.

SMFM

  • Upon review of the evidence, SMFM considers metformin to be a “reasonable and safe first-line pharmacologic alternative to insulin”
  • More data is needed to establish long-term safety of oral agents
  • Glyburide has been associated with adverse neonatal events, such as macrosomia and hypoglycemia but SMFM also acknowledges that “the evidence of benefit of one oral agent over the other remains limited”
  • SMFM does acknowledge that their statement conflicts with ACOG, however

…this difference is based on the values placed by different experts and providers on the evidence available in the medical literature and is not meant to represent an exclusive course of management.

KEY POINTS:

Other ACOG Updates

One abnormal values on the 3 hour OGTT

  • In the previous 2017 practice bulletin, while it was clearly stated that diagnosis of GDM is based on 2 abnormal values on the 3 hour OGTT, ACOG seemed to suggest that one abnormal value may be sufficient to make the diagnosis
  • In the updated 2018 version, ACOG has clarified that statement
    • One abnormal glucose level may warrant a higher level of scrutiny, but is not sufficient for diagnosis
    • More studies are required to determine risk of adverse outcomes and who would benefit from making this a diagnostic criteria

Clarification of insulin use and dosage

  • ACOG has clarified the previous practice bulletin and now states that in women who have abnormal postprandial and fasting glucose levels
    • Insulin starting dose is 0.7-1.0 units/kg daily
    • Dosage should be divided and long-acting or intermediate-acting insulin in combination with short-acting insulin should be used
  • Previously, the 2017 documented stated that insulin was ‘first line’ therapy and the updated document now says ‘preferred’
    • ACOG recognizes that clinicians may assess the clinical circumstances and find the use of oral agents to be a better alternative in women (e.g., patient cannot afford insulin or feel administering the drug would be unsafe)

Macrosomia and cesarean section

  • The recommendation that women with GDM should be counseled about the risks/benefits of a scheduled cesarean section if the estimated fetal weight is ≥4,500 g has been moved from ‘limited or inconsistent scientific evidence’ (Level B) to ‘consensus and expert opinion’ (Level C)

Learn More – Primary Sources:

SMFM Statement Pharmacological treatment of gestational diabetes

ACOG Practice Bulletin 190: Gestational Diabetes Mellitus

CONCEPTT Study: Time for Continuous Glucose Monitoring for All Pregnant Women with Type 1 Diabetes?

BACKGROUND AND PURPOSE:

  1. Continuous glucose monitoring (CGM) provides contemporaneous glucose readings, thus allowing patients to adjust insulin in real-time
  2. Data in non-pregnant women show benefit but conflicting data in pregnancy
  3. Feig et al. (Lancet, 2017) determined the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control compared to capillary glucose monitoring alone

METHODS:

  • Multicenter, open-label, randomized controlled trial (2013-2016)
  • 31 hospital centers in Canada, England, Scotland, Spain, Italy, Ireland, and the USA
  • Women aged 18 to 40 years, with type 1 diabetes for a minimum of 1 year, receiving intensive insulin therapy, and pregnant or planning pregnancy
    • Live singleton fetus confirmed by ultrasound
    • ≤13 weeks and 6 days’ gestation
    • Pregnant: HbA1c between 6.5–10.0% (48–86 mmol/mol)
    • Planning for pregnancy: 7.0–10.0% (53–86 mmol/mol)
  • Ran 2 trials in parallel for (1) pregnant and (2) planning pregnancy
  • In both trials, participants were assigned to the following cohorts
    • Receive CGM in addition to capillary glucose monitoring
    • Receive capillary glucose monitoring
  • Randomization was stratified by insulin delivery and baseline HbA1c
  • Primary outcome was change in HbA1c
    • at 34 weeks’ gestation in pregnant participants
    • at 24 weeks for planning pregnancy participants
  • Secondary outcomes included obstetric and neonatal health outcomes

RESULTS:

  • 325 women were randomized
  • When comparing pregnant CGM users to capillary monitored group, CGM users
    • had a slightly greater change in HbA1c (mean difference -0.19%; 95% CI -0.34 to -0.03; p=0.0207)
    • Spent more time in target range (68% vs 61%; 0.0034)
    • Spent less time hyperglycemic range (27% vs 32%; p= 0.0279)
    • Had comparable hypoglycemic episodes
    • Spent comparable amount of time in hypoglycemic range (3% vs 4%, respectively)
  • Neonatal outcomes in CGM users were significantly improved
    • Lower incidence of large for gestational age (odds ratio [OR] 0.51, 95% CI 0.28 – 0.90; p=0.0210)
    • Fewer NICU admissions lasting more than 24 h (OR 0.48; 95% CI 0.26 – 0.86; p=0.0157)
    • Fewer incidences of neonatal hypoglycemia (OR 0.45; 95% CI 0.22 to 0.89; p=0.0250)
    • 1-day shorter length of hospital stay (p=0.0091)
  • There was no apparent benefit of CGM for women planning pregnancy
  • CGM users had significantly more adverse skin reactions during trials (48% CGM vs 8% control during pregnancy; 44% CGM vs 9% control planning pregnancy)
  • Data was generalizable across centers

CONCLUSION:

  • CGM during pregnancy in patients with type 1 diabetes is linked to improved neonatal outcomes, likely because of better maternal glycemic control and reduced maternal hyperglycemia
  • Number needed to treat (NNT) with CGM
    • 6 pregnant women NNT to prevent one NICU admission
    • 6 pregnant women NNT to prevent one large for gestational age
    • 8 pregnant women NNT to prevent one case of neonatal hypoglycemia
  • The authors conclude that guidelines in type 1 diabetes in pregnancy should be revised to recommend offering CGM to pregnant women with type 1 diabetes using intensive insulin therapy in the first trimester

Learn More – Primary Sources:

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

Updated ACOG Guidance on Gestational Diabetes

SUMMARY:

ACOG released updated guidance on gestational diabetes (GDM), which has become increasingly prevalent worldwide.  Class A1GDM refers to diet-controlled GDM. Class A2GDM refers to the clinical scenario where medications are required. Highlights and changes from the previous practice bulletin include the following:

Screening for GDM – One or Two Step?

  • ACOG (based on NIH consensus panel findings) supports the ‘2 step’ approach (24 – 28 week 1 hour venous glucose measurement following 50g oral glucose solution), followed by a 100g 3 hour oral glucose tolerance test (OGTT) if positive
    • Note: Diagnosis of GDM is based on 2 abnormal values on the 3 hour OGTT
      • ACOG recommends that currently there is insufficient evidence to diagnose GDM based on only one abnormal value
      • Patients with only one elevated value may require additional surveillance
  • 1 step approach (75 g OGTT) on all women will increase the diagnosis of GDM but sufficient prospective studies demonstrating improved outcomes still lacking
  • ACOG does acknowledge that some centers may opt for ‘1 step’ if warranted based on their population
  • ADA considers either 1 step or 2 step (using Coustan Carpenter criteria) to both be valid for GDM diagnosis
  • The USPSTF
    • Recommends screening for gestational diabetes in asymptomatic pregnant persons at ≥24 weeks of gestation or after (B recommendation)
    • Current evidence is insufficient to assess the balance of benefits and harms of screening for gestational diabetes in asymptomatic pregnant persons <24 weeks of gestation (I statement)

Who Should be Screened Early?

ACOG has adopted the NIDDK / ADA guidance on screening for diabetes and prediabetes which takes in to account not only previous pregnancy history but also risk factors associated with type 2 diabetes. Consider early screening in pregnancy if:

Patient is overweight with BMI of 25 (23 in Asian Americans), and one of the following

  • Physical inactivity
  • Known impaired glucose metabolism
  • Previous pregnancy history of:
    • GDM
    • Macrosomia (≥ 4000 g)
    • Stillbirth
  • Hypertension (140/90 mm Hg or being treated for hypertension)
  • HDL cholesterol ≤ 35 mg/dl (0.90 mmol/L)
  • Fasting triglyceride ≥ 250 mg/dL (2.82 mmol/L)
  • PCOS,  acanthosis nigricans, nonalcoholic steatohepatitis, morbid obesity and other conditions associated with insulin resistance
  • Hgb A1C ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose | If A1C>6.5%, diagnosis of pregestational diabetes is met and GCT/GTT not needed
  • Cardiovascular disease
  • Family history of diabetes – 1st degree relative (parent or sibling)
  • Ethnicity of African American, American Indian, Asian American, Hispanic, Latina, or Pacific Islander

(more…)

Practical obstetrics info for your women's healthcare practice

What Is The ‘One-Step’ GDM Screening Approach?

CLINICAL ACTIONS:

There is no debate that all pregnant women should be screened for Gestational Diabetes Mellitus (GDM) between 24 and 28 weeks. However, there are two different approaches to screening for GDM. ACOG currently prefers the traditional ‘two-step’ approach, using an initial screen that, if positive, requires an additional confirmatory test. Alternatively, there is the option of the International Association of Diabetes and Pregnancy Study Groups that recommend a ‘one-step’ approach as follows

  • Perform a 75 g oral glucose tolerance test on all women, after an overnight fast, not previously found to have overt diabetes or GMD earlier in pregnancy
  • Diagnose GDM when one or more of the following plasma glucose values are exceeded
    • Fasting ≥ 92 mg/dL (5.1 mmol/l)
    • 1-hour ≥ 180 mg/dL (10.0 mmol/l)
    • 2-hour ≥ 153 mg/dL (8.5 mmol/l)
  • Early screening for overt diabetes in women at high risk for type 2 diabetes is recommended by this professional group at the first prenatal visit to allow for early detection and management for complications such as fetal anomalies and potential microvascular disease in the mother
    • If fasting plasma glucose is ≥92 mg/dL (≥5.1 mmol/l) but < 126 mg/dL (7.0 mmol/l) diagnose GDM
    • Overt diabetes as per standard cut-offs

SYNOPSIS:

Unfortunately, with the obesity epidemic and more sedentary lifestyles, GDM is increasing as well, and being observed in younger age groups. Complications are significant, including birth trauma to both mother and child. Treatment including diet, increased exercise and if necessary medications can be effective, if GDM is identified in time to implement these changes to achieve best results.

KEY POINTS:

  • ACOG and consensus panel convened by the NIH do not recommend the ‘one-step’ approach, but rather the ‘two-step’ approach
    • Centers can adopt ‘one-step approach’ if more clinically applicable for a particular population
  • The ‘one-step’ screening approach will result in increased diagnosis of GDM
  • The controversy relates to whether with the increased costs and resources necessitated by the ‘one-step’ approach will result in improved outcomes
  • Targeting obesity and improved nutrition can also address macrosomia risks
  • The ADA recognizes ‘2 step’ Carpenter and Coustan approach or ‘1 step’ approach (see Related ObG Topics below) to both be valid for GDM diagnosis

Learn More – Primary Sources:

International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy

NIDDK– Test Criteria for Prediabetes, Diabetes, and Gestational Diabetes

ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus

ADA Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020