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Glycemic Assessment by A1C best evaluated by the combination of re- Correlation Between A1C and Blood
The A1C test is the primary tool for assess- sults from BGM or CGM and A1C. Discor- Glucose Monitoring and Continuous
ing glycemic status in both clinical practice dant results between BGM/CGM and A1C Glucose Monitoring
and clinical trials, and it is strongly linked can be the result of the conditions outlined Table 6.1 provides rough equivalents of
to diabetes complications (2–4). A1C re- above or glycemic variability, with BGM/ A1C and mean glucose levels based on data
flects average glycemia over approxi- CGM missing the extremes. from the international A1C-Derived Average
mately 2–3 months. The performance of As discussed in Section 2, “Diagnosis Glucose (ADAG) study. The ADAG study as-
laboratory tests for A1C is generally and Classification of Diabetes,” there is sessed the correlation between A1C and
excellent for National Glycohemoglobin controversy regarding the clinical signifi- frequent BGM and CGM in 507 adults
Standardization Program (NGSP)–certified cance of racial differences in A1C (9–12). (83% non-Hispanic White) with type 1,
assays (ngsp.org). Thus, A1C testing should There is an emerging understanding of type 2, and no diabetes (19,20). The
be performed routinely in all people with genetic determinants that may modify American Diabetes Association (ADA)
diabetes at initial assessment and as part and the American Association for Clinical
complications (21). BGM is thus an integral CGM is particularly useful in people with dia- range), can provide helpful insights to in-
component of effective therapy for individ- betes who are at risk for hypoglycemia and is form a personalized diabetes management
uals taking insulin. In recent years, CGM commonly used in people with type 1 diabe- plan. Remote access to glucose data is
has become a standard method for glucose tes (21). Use of CGM in type 2 diabetes (as growing and may help improve diabetes
monitoring for most people with type 1 well as in several other forms of diabetes) is management (33–35).
diabetes. Both approaches to glucose mon- growing, especially in people who are taking CGM systems have evolved rapidly in
itoring allow people with diabetes to evalu- insulin. TIR is a useful metric of glycemic sta- both accuracy and affordability. As such,
ate individual responses to therapy and tus. A 10- to 14-day CGM assessment of TIR, many individuals with diabetes have
assess whether glycemic goals are being with CGM wear of 70% or higher, and other these data available to assist with self-
safely achieved. The specific needs and CGM metrics can be used to assess glycemic management and their health care profes-
goals of individuals with diabetes should status and are useful in clinical management sionals’ assessment of glycemic status. Re-
dictate BGM frequency and timing. Please (22–26). TIR, especially mean CGM glucose, ports can be generated from CGM that
refer to Section 7, “Diabetes Technology,” will allow the health care professional and
Table 6.2—Standardized CGM metrics for clinical care in nonpregnant individuals with type 1 or type 2 diabetes
Metric Interpretation Goals
1. Number of days CGM device is worn 14-day wear for pattern
management
2. Percentage of time CGM device is active 70% of data from 14 days
3. Mean glucose Simple average of glucose values *
4. Glucose management indicator Calculated value approximating A1C *
(not always equivalent)
5. Glycemic variability (%CV) target Spread of glucose values #36%†
6. TAR: % of readings and time >250 mg/dL (>13.9 mmol/L) Level 2 hyperglycemia <5% (most adults);
<10% (older adults)
7. TAR: % of readings and time 181–250 mg/dL (10.1–13.9 mmol/L) Level 1 hyperglycemia <25% (most adults);
<50% (older adults)‡
8. TIR: % of readings and time 70–180 mg/dL (3.9–10.0 mmol/L) In range >70% (most adults);
>50% (older adults)
9. TBR: % of readings and time 54–69 mg/dL (3.0–3.8 mmol/L) Level 1 hypoglycemia <4% (most adults);
<1% (older adults)§
10. TBR: % of readings and time <54 mg/dL (<3.0 mmol/L) Level 2 hypoglycemia <1%
CGM, continuous glucose monitoring; CV, coefficient of variation; TAR, time above range; TBR, time below range; TIR, time in range. *Goals
for these values are not standardized. †Some studies suggest that lower %CV targets (<33%) provide additional protection against hypoglyce-
mia for those receiving insulin or sulfonylureas. ‡Goals are for level 1 and level 2 hyperglycemia combined. §Goals are for level 1 and level 2
hypoglycemia combined. Adapted from Battelino et al. (32).
S114 Glycemic Goals and Hypoglycemia Diabetes Care Volume 47, Supplement 1, January 2024
Target 46%
Goal: <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 a standard ambulatory glucose profile (AGP) report. Reprinted from Holt et al. (21).
diabetesjournals.org/care Glycemic Goals and Hypoglycemia S115
Potentially modifiable
safely without significant hypoglycemia Individual needs and preferences
or other adverse effects of treatment. B highly motivated, excellent preference for less
self-care capabilities burdensome therapy
6.7 Less stringent glycemic goals may
be appropriate for individuals with lim- Resources and support
system
ited life expectancy or where the harms readily available limited
of treatment are greater than the ben-
efits. B Figure 6.2—Person and disease factors used to determine optimal glycemic targets. Characteristics and
predicaments toward the left justify more stringent efforts to lower A1C; those toward the right suggest
6.8a Deintensify hypoglycemia-causing less stringent efforts. A1C 7% = 53 mmol/mol. Adapted with permission from Inzucchi et al. (36).
medications (insulin, sulfonylureas, or
meglitinides), or switch to a medica-
with an A1C of <7% (<53 mmol/mol). For Glucose Lowering and Microvascular
tion class with lower hypoglycemia Complications
glycemic goals in older adults, please refer
risk, for individuals who are at high
to Section 13, “Older Adults.” For glyce- Hyperglycemia defines diabetes, and
risk for hypoglycemia, within individu- achieving glycemic goals is fundamental to
mic goals in children, please refer to
alized glycemic goals. B
Section 14, “Children and Adolescents.” diabetes management. The level of chronic
6.8b Deintensify diabetes medications hyperglycemia is the best-established con-
For glycemic goals during pregnancy,
for individuals for whom the harms
please refer to Section 15, “Management comitant risk factor associated with microvas-
and/or burdens of treatment may be cular complications (i.e., diabetic retinopathy,
of Diabetes in Pregnancy.”
greater than the benefits, within indi- nephropathy, and neuropathy). This is best
The health care professional needs to
vidualized glycemic goals. B understood by the fact that nerve, retinal,
work with the individual (as well as with
6.9 Reassess glycemic goals based
family members and caregivers) and should and kidney cells do not require insulin for in-
on the individualized criteria shown
consider adjusting goals for simplifying the tracellular glucose entry. Consequently, these
in Fig. 6.2. E
treatment plan if this change is needed to cells, when exposed to elevated ambient glu-
6.10 Setting a glycemic goal during
improve safety and medication-taking be- cose levels even in the presence of insulin
consultations is likely to improve
havior. Setting specific glycemic (and other) deficiency (absolute or relative), will result in
patient outcomes. E
goals during consultations is likely to improve intracellular metabolic dysfunction and in-
outcomes for individuals with diabetes (37). creased risk of microvascular complications.
For all populations, it is critical that the
glycemic goals be woven into the overall Table 6.3—Summary of glycemic recommendations for many nonpregnant
person-centered strategy (Fig. 6.2) (36). adults with diabetes
For example, less stringent A1C goals are A1C <7.0% (<53 mmol/mol)*†
appropriate for individuals with limited
Preprandial capillary plasma glucose 80–130 mg/dL* (4.4–7.2 mmol/L)
life expectancy and/or significant func-
tional and cognitive impairments. In a Peak postprandial capillary plasma glucose‡ <180 mg/dL* (<10.0 mmol/L)
very young child, safety and simplicity *More or less stringent glycemic goals may be appropriate for individuals. †CGM may be
may outweigh the need for glycemic used to assess glycemic status as noted in Recommendation 6.5b and Fig. 6.1. Goals should
stability in the short run. Recommended be individualized based on duration of diabetes, age/life expectancy, comorbid conditions,
glycemic goals for many nonpregnant known CVD or advanced microvascular complications, hypoglycemia unawareness, and indi-
vidual patient considerations (per Fig. 6.2). ‡Postprandial glucose may be targeted if A1C goals
adults are shown in Table 6.3. The
are not met despite reaching preprandial glucose goals. Postprandial glucose measurements should
recommendations include blood glu- be made 1–2 h after the beginning of the meal, generally peak levels in people with diabetes.
cose levels that appear to correlate
S116 Glycemic Goals and Hypoglycemia Diabetes Care Volume 47, Supplement 1, January 2024
The Diabetes Control and Complications making it possible to maintain glycemic sta- these studies are reviewed extensively in
Trial (DCCT) (38), a prospective randomized tus without the risk of hypoglycemia (see the joint ADA position statement “Intensive
controlled trial of intensive (mean A1C Section 9, “Pharmacologic Approaches to Glycemic Control and the Prevention of
7% [53 mmol/mol]) versus standard Glycemic Treatment”). Moreover, CGM use Cardiovascular Events: Implications of the
(mean A1C 9% [75 mmol/mol]) glycemic was not as common when these trials were ACCORD, ADVANCE, and VA Diabetes
control in people with type 1 diabetes, conducted and automated insulin delivery Trials” (53).
showed definitively that better glycemic systems were not available, which have No significant reduction in composite
status is associated with 50–76% reduc- been shown to improve glucose levels with- CVD events was demonstrated at the end
tions in rates of development and pro- out increasing hypoglycemia. of the intervention in any of these studies,
gression of microvascular complications Among individuals with type 2 diabetes, and ACCORD was stopped prematurely at
(retinopathy, neuropathy, and diabetic three landmark trials (Action to Control 3.5 years because of an increase in total
kidney disease). Follow-up of the DCCT Cardiovascular Risk in Diabetes [ACCORD], mortality, particularly sudden CVD deaths.
cohorts in the Epidemiology of Diabetes Action in Diabetes and Vascular Disease: Serious concerns with the intensive glyce-
outcome of major CVD events, with myocar- more detail in Section 9, “Pharmacologic goals. Less stringent goals (e.g., A1C up to
dial infarctions and heart failure being the Approaches to Glycemic Treatment,” and 8% [64 mmol/mol]) may be recommended
commonest outcomes (57). In contrast, Section 10, “Cardiovascular Disease and if the individual’s life expectancy is such
shorter follow-up of the ADVANCE study Risk Management,” the cardiovascular ben- that the benefits of an intensive goal may
in the Action in Diabetes and Vascular Dis- efits of SGLT2 inhibitors or GLP-1 receptor not be realized or if the risks and burdens
ease Preterax and Diamicron MR Con- agonists are not contingent upon A1C low- outweigh the potential benefits. Severe or
trolled Evaluation Post Trial Observational ering; therefore, initiation can be consid- frequent hypoglycemia is an absolute indi-
Study (ADVANCE-ON) demonstrated no sig- ered in people with type 2 diabetes and cation for the modification of treatment
nificant effect on CVD events (59). Even in CVD independent of the current A1C or plans, including setting higher glycemic
the epidemiological follow-up of ACCORD A1C goal or metformin therapy. Based on goals.
in the Action to Control Cardiovascular Risk these considerations, the following two Diabetes is a chronic disease that pro-
in Diabetes Follow-On Study (ACCORDION), strategies are offered (63): gresses over decades. Thus, a goal that
the excess increase in total mortality that might be appropriate for an individual
for alternative medications (e.g., use of Glucagon preparations that do not a measured glucose level <70 mg/dL
SGLT2 inhibitors in the setting of heart have to be reconstituted are pre- (<3.9 mmol/L) is considered clinically im-
failure or diabetic kidney disease and use ferred. E portant, regardless of symptoms. Level 2
of GLP-1 receptor agonists in the setting 6.14 All individuals taking insulin A hypoglycemia (defined as a blood glucose
of CVD or obesity). Clinicians should also or at risk for hypoglycemia C should concentration <54 mg/dL [<3.0 mmol/L])
consider medication burdens other than receive structured education for hy- is the threshold at which neuroglycopenic
hypoglycemia, including tolerability, difficul- poglycemia prevention and treat- symptoms begin to occur and requires im-
ties of administration, impact on education ment, with ongoing education for mediate action to resolve the hypoglyce-
or employment, and financial cost. These those who experience hypoglycemic mic event. If an individual has level 2
factors should be balanced against bene- events. hypoglycemia without adrenergic or neu-
fits from glycemic lowering and disease- 6.15 One or more episodes of level 2 roglycopenic symptoms, they likely have
specific benefits of newer medications impaired hypoglycemia awareness (dis-
or 3 hypoglycemia should prompt
that may be independent of glycemic cussed further in HYPOGLYCENMIA RISK ASSESSMENT,
are), and follow up positive responses with activity management, medication adjust- be a health care professional to safely ad-
a more detailed evaluation (105,110). ment, glucose monitoring, and routine clinical minister glucagon. Those in close contact
Other notable clinical and biological risk surveillance may improve outcomes (105). with, or having custodial care of, these in-
factors for hypoglycemia are older age, mul- CGM with automated low-glucose suspend dividuals (family members, roommates,
timorbidity, cognitive impairment, chronic and automated insulin delivery systems have school personnel, childcare professionals,
kidney disease and end-stage kidney dis- been shown to be effective in reducing hypo- correctional institution staff, or coworkers)
ease in particular, CVD, depression, and glycemia in type 1 diabetes (117). For people should be instructed on the use of gluca-
neuropathy (92,93). Female sex has also with type 1 diabetes with level 3 hypoglyce- gon, including where the glucagon product
been found to be an independent risk fac- mia and hypoglycemia unawareness that per- is kept and when and how to administer it.
tor for hypoglycemia in multiple studies, al- sists despite medical treatment, human islet It is essential that they be explicitly edu-
though the mechanisms of this relationship transplantation may be an option, but the ap- cated to never administer insulin to individ-
are unclear and require further research proach remains experimental (118,119). uals experiencing hypoglycemia. Glucagon
(92). Cognitive impairment has a strong bi-
such as fasting as part of religious obser- tein may increase insulin secretion and patient education for hypoglycemia pre-
vance. Fasting may increase the risk for hy- should not be used to treat hypoglycemia vention and treatment is critical and has
poglycemia among individuals treated (124). Ongoing insulin activity or insulin been shown to improve hypoglycemia
with insulin or insulin secretagogues if not secretagogues may lead to recurrent hypo- outcomes (131,132). Education should
properly planned for, so clinicians need to glycemia unless more food is ingested after ideally be provided through a diabetes
engage these individuals to codevelop a di- recovery. self-management education and support
abetes treatment plan that is safe and re- program or by a trained diabetes educa-
spectful of their traditions (114). Glucagon tor, although these services are not avail-
Young children with type 1 diabetes and The use of glucagon is indicated for the able in many areas (133,134). If structured
the elderly, including those with type 1 and treatment of hypoglycemia in people un- education is not available, clinicians should
type 2 diabetes (115,116), are noted as be- able or unwilling to consume carbohy- educate individuals at risk for hypoglyce-
ing particularly vulnerable to hypoglycemia drates by mouth. All individuals treated mia on hypoglycemia definitions, situa-
because of their reduced ability to recognize with insulin or who are at high risk of hypo- tions that may precipitate hypoglycemia
hypoglycemic symptoms and effectively glycemia as discussed above should be pre- (fasting, delayed meals, physical activity,
communicate their needs. Individualized scribed glucagon. For these individuals, and illness), blood glucose self-monitoring,
glycemic goals, patient education, nutrition clinicians should routinely review their ac- avoidance of driving with hypoglycemia, step-
intervention (e.g., bedtime snack to prevent cess to glucagon, as appropriate glucagon by-step instructions on hypoglycemia treat-
overnight hypoglycemia when specifically prescribing is very low in current practice ment as discussed above, and glucagon use
needed to treat low blood glucose), physical (125,126). An individual does not need to as appropriate (131).
diabetesjournals.org/care Glycemic Goals and Hypoglycemia S121
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