Professional Documents
Culture Documents
6. GLYCEMIC TARGETS
cludes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guide-
lines, and tools to evaluate quality of care. Members of the ADA Professional
Practice Committee, a multidisciplinary expert committee, are responsible for up-
dating the Standards of Care annually, or more frequently as warranted. For a de-
tailed description of ADA standards, statements, and reports, as well as the
evidence-grading system for ADA’s clinical practice recommendations and a full
list of Professional Practice Committee members, please refer to Introduction
and Methodology. Readers who wish to comment on the Standards of Care are
invited to do so at professional.diabetes.org/SOC.
Glycemic Assessment
Recommendations
6.1 Assess glycemic status (A1C or other glycemic measurement such as time Disclosure information for each author is
in range or glucose management indicator) at least two times a year in available at https://doi.org/10.2337/dc23-SDIS.
patients who are meeting treatment goals (and who have stable glycemic Suggested citation: ElSayed NA, Aleppo G, Aroda
control). E VR, et al., American Diabetes Association. 6.
6.2 Assess glycemic status at least quarterly and as needed in patients whose Glycemic targets: Standards of Care in Diabetes—
2023. Diabetes Care 2023;46(Suppl. 1):S97–S110
therapy has recently changed and/or who are not meeting glycemic
goals. E © 2022 by the American Diabetes Association.
Readers may use this article as long as the
work is properly cited, the use is educational
and not for profit, and the work is not altered.
A1C reflects average glycemia over approximately 3 months. The performance of the More information is available at https://www.
test is generally excellent for National Glycohemoglobin Standardization Program diabetesjournals.org/journals/pages/license.
S98 Glycemic Targets Diabetes Care Volume 46, Supplement 1, January 2023
(NGSP)-certified assays (ngsp.org). The most assays in use in the U.S. are accu-
Table 6.1—Estimated average glucose
test is the primary tool for assessing gly- rate in individuals who are heterozygous (eAG)
cemic control and has a strong predictive for the most common variants (ngsp.
A1C (%) mg/dL* mmol/L
value for diabetes complications (2–4). org/interf.asp). Other measures of aver-
5 97 (76–120) 5.4 (4.2–6.7)
Thus, A1C testing should be performed age glycemia such as fructosamine and
routinely in all people with diabetes at 1,5-anhydroglucitol are available, but 6 126 (100–152) 7.0 (5.5–8.5)
initial assessment and as part of continu- their translation into average glucose 7 154 (123–185) 8.6 (6.8–10.3)
ing care. Measurement approximately levels and their prognostic significance 8 183 (147–217) 10.2 (8.1–12.1)
every 3 months determines whether pa- are not as clear as for A1C and CGM.
tients’ glycemic targets have been reached Though some variability in the relation- 9 212 (170–249) 11.8 (9.4–13.9)
and maintained. A 14-day CGM assess- ship between average glucose levels 10 240 (193–282) 13.4 (10.7–15.7)
70 Low 5%
54
10% Goal: <4% Glucose Variability ............................................ 45.5%
Very Low 5%
Goal: <36%
Goal: <1% Each 1% time in range = ~15 minutes
AGP is a summary of glucose values from the report period, with median (50%) and other percentiles shown as if they occurred in a single day.
350
mg/dL
95%
75%
250
50%
25%
180
Target
Range
70 5%
54
0
12am 3am 6am 9am 12pm 3pm 6pm 9pm 12am
180
70
180
70
Figure 6.1—Key points included in standard ambulatory glucose profile (AGP) report. Reprinted from Holt et al. (34).
diabetesjournals.org/care Glycemic Targets S101
assess hypoglycemia, hyperglycemia, and parallel goal for many nonpreg- glycemic separation between the treat-
glycemic variability. As discussed in a re- nant adults is time in range of ment groups diminished and disap-
cent consensus document, a report for- peared during follow-up.
>70% with time below range
matted as shown in Fig. 6.1 can be The Kumamoto Study (44) and UK
<4% and time <54 mg/dL
generated (35). Published data from two Prospective Diabetes Study (UKPDS)
<1%. For those with frailty or
retrospective studies suggest a strong cor- (45,46) confirmed that intensive gly-
at high risk of hypoglycemia, a
relation between TIR and A1C, with a cemic control significantly decreased
target of >50% time in range
goal of 70% TIR aligning with an A1C of rates of microvascular complications
with <1% time below range
7% (8,26). Note the goals of therapy in people with short-duration type 2
is recommended. (See Fig. 6.1
next to each metric in Fig. 6.1 (e.g., low, diabetes. Long-term follow-up of the
and Table 6.2.) B
<4%; very low, <1%) as values to guide UKPDS cohorts showed enduring ef-
Potentially modifiable
Patient preference betes being diagnosed at <40 years of
highly motivated, excellent preference for less
self-care capabilities burdensome therapy
age and a demonstrably increased bur-
den of heart disease and years of life
Resources and support
system
lost in people diagnosed at a younger
readily available limited age (57–60). Thus, to prevent both mi-
crovascular and macrovascular compli-
Figure 6.2—Patient and disease factors used to determine optimal glycemic targets. Character- cations of diabetes, there is a major call
istics and predicaments toward the left justify more stringent efforts to lower A1C; those to-
ward the right suggest less stringent efforts. A1C 7% = 53 mmol/mol. Adapted with permission to overcome therapeutic inertia and
from Inzucchi et al. (71). treat to target for an individual patient
(60,61). During the UKPDS, there was a
16% reduction in CVD events (combined
risk. These trials showed that lower higher versus lower A1C; therefore, fatal or nonfatal MI and sudden death)
A1C levels were associated with reduced beyond post hoc analysis of these tri- in the intensive glycemic control arm
onset or progression of some micro- als, we do not have evidence that it is that did not reach statistical significance
vascular complications (50–52). the glucose lowering by these agents that (P = 0.052), and there was no sugges-
The concerning mortality findings confers the CVD and renal benefit (53). tion of benefit on other CVD outcomes
in the ACCORD trial discussed below As such, based on clinician judgment and (e.g., stroke). Similar to the DCCT/EDIC,
and the relatively intense efforts re- patient preferences, select patients, espe- after 10 years of observational follow-
quired to achieve near euglycemia should cially those with little comorbidity and a up, those originally randomized to in-
also be considered when setting gly- long life expectancy, may benefit from tensive glycemic control had significant
cemic targets for individuals with long- adopting more intensive glycemic targets long-term reductions in MI (15% with
standing diabetes, such as those popula- if they can achieve them safely and with- sulfonylurea or insulin as initial pharma-
tions studied in ACCORD, ADVANCE, and out hypoglycemia or significant thera- cotherapy, 33% with metformin as ini-
VADT. Findings from these studies sug- peutic burden. tial pharmacotherapy) and in all-cause
gest caution is needed in treating diabe- mortality (13% and 27%, respectively)
tes to near-normal A1C goals in people A1C and Cardiovascular Disease (47).
with long-standing type 2 diabetes with Outcomes ACCORD, ADVANCE, and VADT sug-
or at significant risk of CVD. Cardiovascular Disease and Type 1 Diabetes gested no significant reduction in CVD
These landmark studies need to be CVD is a more common cause of death outcomes with intensive glycemic control
considered with an important caveat; than microvascular complications in pop- in participants followed for shorter dura-
glucagon-like peptide 1 (GLP-1) receptor ulations with diabetes. There is evidence tions (3.5–5.6 years) and who had more
agonists and sodium–glucose cotrans- for a cardiovascular benefit of intensive advanced type 2 diabetes and CVD risk
porter 2 (SGLT2) inhibitors were not ap- glycemic control after long-term follow- than the UKPDS participants. All three tri-
proved at the time of these trials. As up of cohorts treated early in the course als were conducted in relatively older par-
such, these agents with established car- of type 1 diabetes. In the DCCT, there ticipants with a longer known duration
diovascular and renal benefits appear to was a trend toward lower risk of CVD of diabetes (mean duration 8–11 years)
be safe and beneficial in this group of events with intensive control. In the and either CVD or multiple cardio-
individuals at high risk for cardiorenal 9-year post-DCCT follow-up of the vascular risk factors. The target A1C
complications. Randomized clinical trials EDIC cohort, participants previously among intensive-control participants
examining these agents for cardiovas- randomized to the intensive arm had was <6% (42 mmol/mol) in ACCORD,
cular safety were not designed to test a significant 57% reduction in the risk <6.5% (48 mmol/mol) in ADVANCE,
diabetesjournals.org/care Glycemic Targets S103
and a 1.5% reduction in A1C compared and mortality (69). Therefore, health engage people with type 1 and type 2 di-
with control participants in VADT, care professionals should be vigilant abetes in shared decision-making. More
with achieved A1C of 6.4% vs. 7.5% in preventing hypoglycemia and should aggressive targets may be recommended
(46 mmol/mol vs. 58 mmol/mol) in not aggressively attempt to achieve if they can be achieved safely and
ACCORD, 6.5% vs. 7.3% (48 mmol/mol near-normal A1C levels in people in with an acceptable burden of therapy
vs. 56 mmol/mol) in ADVANCE, and 6.9% whom such targets cannot be safely and if life expectancy is sufficient to
vs. 8.4% (52 mmol/mol vs. 68 mmol/mol) and reasonably achieved. As discussed reap the benefits of stringent targets.
in VADT. Details of these studies are in Section 9, “Pharmacologic Approaches Less stringent targets (A1C up to 8%
reviewed extensively in the joint ADA to Glycemic Treatment,” addition of spe- [64 mmol/mol]) may be recommended
position statement “Intensive Glycemic cific SGLT2 inhibitors or GLP-1 receptor if the patient’s life expectancy is such
Control and the Prevention of Cardio- agonists that have demonstrated CVD that the benefits of an intensive goal
Table 6.3—Summary of glycemic recommendations for many nonpregnant hypoglycemia avoidance educa-
adults with diabetes tion and reevaluation and ad-
A1C <7.0% (53 mmol/mol)*# justment of the treatment plan
Preprandial capillary plasma glucose 80–130 mg/dL* (4.4–7.2 mmol/L) to decrease hypoglycemia. E
6.14 Insulin-treated patients with hy-
Peak postprandial capillary plasma glucose† <180 mg/dL* (10.0 mmol/L)
poglycemia unawareness, one
*More or less stringent glycemic goals may be appropriate for individual patients. #CGM level 3 hypoglycemic event, or a
may be used to assess glycemic target as noted in Recommendation 6.5b and Fig. 6.1. pattern of unexplained level 2
Goals should be individualized based on duration of diabetes, age/life expectancy, comorbid
hypoglycemia should be advised
conditions, known CVD or advanced microvascular complications, hypoglycemia unaware-
ness, and individual patient considerations (as per Fig. 6.2). †Postprandial glucose may be to raise their glycemic targets
administer glucagon. In addition to tra- diabetes (106). Hence, individuals with insulin dosing can improve A1C with
ditional glucagon injection powder that one or more episodes of clinically signifi- minimal hypoglycemia (133,134).
requires reconstitution prior to injec- cant hypoglycemia may benefit from at
tion, intranasal glucagon and ready-to- least short-term relaxation of glycemic INTERCURRENT ILLNESS
inject glucagon preparations for sub- targets and availability of glucagon (107).
For further information on management
cutaneous injection are available and Any person with recurrent hypoglycemia
may be beneficial in view of safety, ef- or hypoglycemia unawareness should of individuals with hyperglycemia in the
ficacy, and ease of use. Care should be have their glucose management treat- hospital, see Section 16, “Diabetes Care
taken to ensure that glucagon products ment plan adjusted. in the Hospital.”
are not expired (102). Stressful events (e.g., illness, trauma,
Use of CGM Technology in Hypoglycemia surgery) may worsen glycemic control and
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