ADA 2018 Standards of Care

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diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf

Section 6. Glycemic Targets
Based on new data, the recommendation for the use of continuous glucose monitor- ing (CGM) in adults with type 1 diabetes is no longer limited to those ages 25 and above but has been expanded to all adults (18 and above) who are not meeting glyce- mic targets.
Additional text was added about a new intermittent or “flash” CGM device that was recently approved for adult use.
Details were added about new CGM de- vices that no longer require confirmatory self-monitoring of blood glucose for treat- ment decisions.
As in Section 2, this section now includes an expanded discussion of the limitations of A1C in certain populations based on the presence of hemoglobin variants, differ- ences in red blood cell turnover rates, eth- nicity, and age.
To clarify the classification of hypogly- cemia, level 1 hypoglycemia was renamed “hypoglycemia alert value” from “glucose alert value.”

Confirming the Diagnosis
Unless there is a clear clinical diagnosis (e.g., patient in a hyperglycemic crisis or with classic symptoms of hyperglyce- mia and a random plasma glucose $200 mg/dL [11.1 mmol/L]), a second test is required for confirmation. It is recom- mended that the same test be repeated or a different test be performed without delay using a new blood sample for con- firmation. For example, if the A1C is 7.0% (53 mmol/mol) and a repeat result is 6.8% (51 mmol/mol), the diagnosis of diabetes is confirmed. If two different tests (such as A1C and FPG) are both above the di- agnostic threshold, this also confirms the diagnosis. On the other hand, if a pa- tient has discordant results from two different tests, then the test result that is above the diagnostic cut point should be repeated, with consideration of the possibility of A1C assay interference. The diagnosis is made on the basis of the con- firmed test. For example, if a patient meets the diabetes criterion of the A1C (two results $6.5% [48 mmol/mol]) but not FPG (,126 mg/dL [7.0 mmol/L]), that per- son should nevertheless be considered to have diabetes.
Since all the tests have preanalytic and analytic variability, it is possible that an abnormal result (i.e., above the diagnostic threshold), when repeated, will produce a value below the diagnostic cut point. This scenario is likely for FPG and 2-h PG if the glucose samples remain at room temper- ature and are not centrifuged promptly. Because of the potential for preanalytic variability, it is critical that samples for plasma glucose be spun and separated immediately after they are drawn. If pa- tients have test results near the margins of the diagnostic threshold, the health care professional should follow the patient closely and repeat the test in 3–6 months.

ASSESSMENT OF GLYCEMIC CONTROL
Patient self-monitoring of blood glucose (SMBG) and A1C are available to health care providers and patients to assess the effectiveness and safety of a manage- ment plan on glycemic control. Continuous glucose monitoring (CGM) also has an important role in assessing the effectiveness and safety of treatment in sub- groups of patients with type 1 diabetes and in selected patients with type 2 di- abetes. Data indicate similar A1C and safety with the use of CGM compared with SMBG (1).

Recommendations
- Most patients using intensive insulin regimens (multiple-dose insulin or in- sulin pump therapy) should perform self-monitoring of blood glucose (SMBG) prior to meals and snacks, at bedtime, occasionally postprandially, prior to exercise, when they suspect low blood glucose, after treating low blood glucose until they are normoglycemic, and prior to critical tasks such as driving. B
- When prescribed as part of a broad educational program, SMBG may help to guide treatment decisions and/or self-management for patients taking less fre- quent insulin injections B or noninsulin therapies. E
-  When prescribing SMBG, ensure that patients receive ongoing instruction and regular evaluation of SMBG technique, SMBG results, and their ability to use SMBG data to adjust therapy. E
c When used properly, continuous glucose monitoring (CGM) in conjunction with intensive insulin regimens is a useful tool to lower A1C in adults with type 1 diabetes who are not meeting glycemic targets. A
- CGM may be a useful tool in those with hypoglycemia unawareness and/or frequent hypoglycemic episodes. C
- Given the variable adherence to CGM, assess individual readiness for continuing CGM use prior to prescribing. E

Although performed with older gener- ation CGM devices, a 26-week random- ized trial of 322 patients with type 1 diabetes showed that adults aged $25 years using intensive insulin therapy and CGM experienced a 0.5% reduction in A1C (from ;7.6% to 7.1% [;60 mmol/mol to 54 mmol/mol]) compared with those using intensive insulin therapy with SMBG (21). The greatest predictor of A1C lower- ing for all age-groups was frequency of sensor use, which was highest in those aged $25 years and lower in younger age-groups. Two clinical trials in adults with type 1 diabetes not meeting A1C targets and using multiple daily injections also found that the use of CGM compared with usual care resulted in lower A1C levels than SMBG over 24–26 weeks (22,23). Other small, short-term studies have demonstrated similar A1C reductions us- ing CGM compared with SMBG in adults with A1C levels $7% (53 mmol/mol) (24,25).

In a recent report, mean glucose measured with CGM versus central labo- ratory–measured A1C in 387 participants in three randomized trials demonstrated that A1C may underestimate or overesti- mate mean glucose. Thus, as suggested, a patient’s CGM profile has considerable potential for optimizing his or her glyce- mic management (42).

Recommendations
- A reasonable A1C goal for many nonpregnant adults is ,7% (53 mmol/mol). A
- Providers might reasonably suggest more stringent A1C goals (such as ,6.5% [48 mmol/mol]) for se- lected individual patients if this
can be achieved without significant hypoglycemia or other adverse ef- fects of treatment (i.e., polyphar- macy). Appropriate patients might include those with short duration of diabetes, type 2 diabetes treated with lifestyle or metformin only, long life expectancy, or no signifi- cant cardiovascular disease. C
- Less stringent A1C goals (such as ,8% [64 mmol/mol]) may be ap- propriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascu- lar or macrovascular complications, extensive comorbid conditions, or long-standing diabetes in whom the goal is difficult to achieve de- spite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin. B

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Insulin Therapy
Insulin is the mainstay of therapy for individuals with type 1 diabetes. Generally, the starting insulin dose is based on weight, with doses ranging from 0.4 to 1.0 units/kg/day of total insulin with higher amounts required during puberty. The American Diabetes Association/JDRF Type 1 Diabetes Sourcebook notes 0.5 units/kg/day as a typical starting dose in patients with type 1 diabetes who are metabolically stable, with higher weight-based dosing required immediately following presentation with ketoacidosis (1), and provides detailed information on intensification of therapy to meet individualized needs. The American Diabetes Association (ADA) position statement “Type 1 Diabetes Management Through the Life Span” additionally provides a thorough overview of type 1 diabetes treatment (2).

Education regarding matching prandial insulin dosing to carbohydrate intake, premeal glucose levels, and anticipated activity should be considered, and se- lected individuals who have mastered carbohydrate counting should be edu- cated on fat and protein gram estimation (3–5). Although most studies of multiple daily injections versus continuous subcu- taneous insulin infusion (CSII) have been small and of short duration, a systematic review and meta-analysis concluded that there are minimal differences between the two forms of intensive insulin therapy in A1C (combined mean between-group difference favoring insulin pump therapy –0.30% [95% CI –0.58 to –0.02]) and se- vere hypoglycemia rates in children and adults (6). A 3-month randomized trial in patients with type 1 diabetes with noctur- nal hypoglycemia reported that sensor- augmented insulin pump therapy with the threshold suspend feature reduced nocturnal hypoglycemia without increas- ing glycated hemoglobin levels (7). The U.S. Food and Drug Administration (FDA) has also approved the first hybrid closed- loop system pump. The safety and effi- cacy of hybrid closed-loop systems has been supported in the literature in ado- lescents and adults with type 1 diabetes (8,9).
Intensive management using CSII and continuous glucose monitoring should be encouraged in selected patients when there is active patient/family participa- tion (10–12).
The Diabetes Control and Complica- tions Trial (DCCT) clearly showed that in- tensive therapy with multiple daily injections or CSII delivered by multidisci- plinary teams of physicians, nurses, dieti- tians, and behavioral scientists improved glycemia and resulted in better long-term outcomes (13–15). The study was carried out with short-acting and intermediate- acting human insulins. Despite better mi- crovascular, macrovascular, and all-cause mortality outcomes, intensive therapy was associated with a high rate of severe hypoglycemia (61 episodes per 100 patient- years of therapy). Since the DCCT, a number of rapid-acting and long-acting insulin an- alogs have been developed. These analogs are associated with less hypoglycemia, less weight gain, and lower A1C than human insulins in people with type 1 diabetes (16–18). Longer-acting basal analogs (U-300 glargine or degludec) may addi- tionally convey a lower hypoglycemia risk

compared with U-100 glargine in patients with type 1 diabetes (19,20).
Rapid-acting inhaled insulin used be- fore meals in patients with type 1 diabe- tes was shown to be noninferior when compared with aspart insulin for A1C low- ering, with less hypoglycemia observed with inhaled insulin therapy (21). How- ever, the mean reduction in A1C was greater with aspart (–0.21% vs. –0.40%, satisfying the noninferiority margin of 0.4%), and more patients in the insulin aspart group achieved A1C goals of #7.0% (53 mmol/mol) and #6.5% (48 mmol/mol). Because inhaled insulin car- tridges are only available in 4-, 8-, and 12-unit doses, limited dosing increments to fine-tune prandial insulin doses in type 1 diabetes are a potential limitation.

*{The above is in the 2018 standards of care? } 

Postprandial glucose excursions may be better controlled by adjusting the tim- ing of prandial (bolus) insulin dose admin- istration. The optimal time to administer prandial insulin varies, based on the type of insulin used (regular, rapid-acting ana- log, inhaled, etc.), measured blood glucose level, timing of meals, and carbohydrate consumption. Recommendations for pran- dial insulin dose administration should therefore be individualized.

[dh4mizzou]

Peppy,

I'm more than a little disturbed that they state "add 1 rapid-acting insulin INJECTION before largest meal". I wish they had just removed that word from the equation.

IIRC this points someone directly to FIASP without even considering AFREZZA. I believe this is the kind of stuff that Dr. Kendall needs to address.

[mnholdem]

"...intensive therapy was associated with a high rate of severe hypoglycemia (61 episodes per 100 patient- years of therapy). Since the DCCT, a number of rapid-acting and long-acting insulin analogs have been developed. These analogs are associated with less hypoglycemia, less weight gain, and lower A1C than human insulins in people with type 1 diabetes..."

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Diabetes Control and Complications Trial (DCCT)

DCCT Results

The DCCT showed that people with type 1 diabetes who kept their blood glucose levels as close to normal as safely possible with intensive diabetes treatment as early as possible in their disease had fewer diabetes-related health problems after 6.5 years, compared to people who used the conventional treatment.

DCCT showed that people who used intensive treatment lowered their risk of

• diabetic eye disease by 76 percent; and advancement of eye disease by about half (54 percent), in people with some eye disease at the beginning of the study.
• diabetic kidney disease by 50 percent.
• diabetic nerve disease by 60 percent.

Researchers were not able to show whether people who used intensive treatment lowered their risk of heart disease during the DCCT, since only a few people had heart disease during the study.

Participants who used intensive treatment had an average A1C of 7 percent, while participants who used the conventional treatment had an average A1C of 9 percent. The A1C blood test shows a person’s average blood glucose levels over the previous 2 to 3 months. A normal A1C value is 6 percent or less.

In the DCCT, the major side effect of intensive treatment was a higher risk for hypoglycemia, also called low blood glucose, which can be deadly if not treated immediately. Participants knew how to treat hypoglycemia.

The Diabetes Control and Complications Trial (DCCT) took place from 1983 to 1993. The study involved 1,441 volunteers ages 13 to 39, and took place in 29 medical centers in the United States and Canada. At the start of the DCCT, participants had type 1 diabetes for at least 1 year but no longer than 15 years, and had no or only early signs of diabetic eye or kidney diseases.

Source: www.niddk.nih.gov/about-niddk/research-areas/diabetes/blood-glucose-control-studies-type-1-diabetes-dcct-edic

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The fact that the ADA Standard of Care for Diabetes references the hypoglycemic dangers of intensive insulin therapy based on a study that is more than 30 years old is a excellent example of how out-of-touch the American Diabetes Association is in their recommendations of diabetes treatments. They do acknowledge that since DCCT rapid-acting analogs have been developed which are associated with less hypoglycemia but, of course, there is no mention of ultra-rapid acting inhaled insulin, which is NOT an analog insulin and is much faster with less hypoglycemic risk.

IMHO, MannKind's CMO David Kendall MD is correct in his assessment that current practices for treating diabetes are antiquated and barbaric.

Is it any wonder that diabetes is currently the most costly disease in the USA?

[mango]

The ADA does not follow the scientific method. And "Consensus" has no place in science. It is political quackery.

[peppy]

PHARMACOLOGIC THERAPY FOR TYPE 2 DIABETES

Metformin may be safely used in patients with estimated glomerular filtra- tion rate (eGFR) as low as 30 mL/min/ 1.73 m2, and the FDA recently revised the label for metformin to reflect its safety in patients with eGFR $30 mL/ min/1.73 m2 (34). Patients should be ad- vised to stop the medication in cases of nausea, vomiting, or dehydration. Met- formin is associated with vitamin B12 deficiency, with a recent report from the Diabetes Prevention Program Outcomes Study (DPPOS) suggesting that periodic testing of vitamin B12 levels should be considered in metformin-treated pa- tients, especially in those with anemia or peripheral neuropathy (35).
In patients with metformin contrain- dications or intolerance, consider an ini- tial drug from another class depicted in Fig. 8.1 under “Dual Therapy” and pro- ceed accordingly. When A1C is $9% (75 mmol/mol), consider initiating dual com- bination therapy (Fig. 8.1) to more expe- ditiously achieve the target A1C level. Insulin has the advantage of being effec- tive where other agents may not be and should be considered as part of any com- bination regimen when hyperglycemia is severe, especially if catabolic features (weight loss, ketosis) are present.

Con- sider initiating combination insulin in- jectable therapy (Fig. 8.2) when blood glucose is $300 mg/dL (16.7 mmol/L) or A1C is $10% (86 mmol/mol) or if the pa- tient has symptoms of hyperglycemia (i.e., polyuria or polydipsia). As the pa- tient’s glucose toxicity resolves, the regi- men may, potentially, be simplified.
Combination Therapy
Although there are numerous trials comparing dual therapy with metformin alone, few directly compare drugs as add- on therapy. A comparative effectiveness meta-analysis (36) suggests that each new class of noninsulin agents added to initial therapy generally lowers A1C ap- proximately 0.7–1.0%. If the A1C target is not achieved after approximately 3 months and patient does not have atherosclerotic cardiovascular disease (ASCVD), consider a combination of metformin and any one of the preferred six treatment options: sulfonylurea, thiazolidinedione, DPP-4
Recommendations
c Metformin, if not contraindicated and if tolerated, is the preferred ini- tial pharmacologic agent for the treatment of type 2 diabetes. A
c Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic mea- surement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with ane- mia or peripheral neuropathy. B
- Consider initiating insulin therapy (with or without additional agents) in patients with newly diagnosed type 2 diabetes who are symptom- atic and/or have A1C $10% (86 mmol/mol) and/or blood glucose levels $300 mg/dL (16.7 mmol/L). E
 - Consider initiating dual therapy in patients with newly diagnosed type 2 diabetes who have A1C $9% (75 mmol/mol). E

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Notice that every category has a warning. Many with Black Box warnings.

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Summary of Revisions: Standards of Medical Care in Diabetes—2018
care.diabetesjournals.org/content/41/Supplement_1/S4

the Standards of Care will now become the ADA’s sole source of clinical practice recommendations, superseding all prior position and scientific statements. The change is intended to clarify the Association’s current positions by consolidating all clinical practice recommendations into the Standards of Care. For further information on changes to the classification and definitions of ADA Standards of Care, statements, reports, and reviews, see the Introduction.

Section 6. Glycemic Targets

Based on new data, the recommendation for the use of continuous glucose monitoring (CGM) in adults with type 1 diabetes is no longer limited to those ages 25 and above but has been expanded to all adults (18 and above) who are not meeting glycemic targets.

Additional text was added about a new intermittent or “flash” CGM device that was recently approved for adult use.

Details were added about new CGM devices that no longer require confirmatory self-monitoring of blood glucose for treatment decisions.

As in Section 2, this section now includes an expanded discussion of the limitations of A1C in certain populations based on the presence of hemoglobin variants, differences in red blood cell turnover rates, ethnicity, and age.

To clarify the classification of hypoglycemia, level 1 hypoglycemia was renamed “hypoglycemia alert value” from “glucose alert value.”

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Standards of Care
This document is an official ADA position, is authored by the ADA, and provides all of the ADA’s current clinical practice rec- ommendations. To update the Standards of Care, the ADA’s Professional Practice Committee (PPC) performs an extensive clinical diabetes literature search, supple- mented with input from ADA staff and the medical community at large. The PPC up- dates the Standards of Care annually, or more frequently online should the PPC determine that new evidence or regula- tory changes (e.g., drug approvals, label changes) merit immediate incorporation. The Standards of Care supersedes all pre- vious ADA position statementsdand the recommendations thereindon clinical topics within the purview of the Stand- ards of Care; ADA position statements, while still containing valuable analyses, should not be considered the ADA’s current position. The Standards of Care receives annual review and approval by the ADA Board of Directors.

diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf
S1

GENERAL CHANGES
The field of diabetes care is rapidly changing as new research, technology, and treat- ments that can improve the health and well-being of people with diabetes continue to emerge. With annual updates since 1989, the American Diabetes Association’s (ADA’s) “Standards of Medical Care in Diabetes” (Standards of Care) has long been a leader in producing guidelines that capture the most current state of the field. Starting in 2018, the ADA will update the Standards of Care even more frequently online should the Professional Practice Committee de- termine that new evidence or regulatory changes merit immediate incorporation into the Standards of Care. In addition, the Standards of Care will now become the ADA’s sole source of clinical practice recommendations, superseding all prior position and scientific statements.

[mannmade]

Unleash the Kraken... I mean Dr. K

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To provide a second set of cost infor- mation for antihyperglycemic agents, NADAC data was added to the average wholesale prices information in Table 8.3 and Table 8.4.  pg S5

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Hyperglycemia
In those with type 2 diabetes, the degree and duration of hyperglycemia are re- lated to dementia. More rapid cognitive decline is associated with both increased A1C and longer duration of diabetes (34). The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study found that each 1% higher A1C level was associated with lower cognitive function in individu- als with type 2 diabetes (35). However, the ACCORD study found no difference in cognitive outcomes in participants ran- domly assigned to intensive and standard glycemic control, supporting the recom- mendation that intensive glucose control should not be advised for the improve- ment of cognitive function in individuals with type 2 diabetes (36).

Hypoglycemia
In type 2 diabetes, severe hypoglycemia is associated with reduced cognitive func- tion, and those with poor cognitive func- tion have more severe hypoglycemia. In a long-term study of older patients with type 2 diabetes, individuals with one or more recorded episode of severe hypo- glycemia had a stepwise increase in risk of dementia (37). Likewise, the ACCORD trial found that as cognitive function de- creased, the risk of severe hypoglycemia increased (38). Tailoring glycemic therapy may help to prevent hypoglycemia in in- dividuals with cognitive dysfunction.

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Rapid-acting inhaled insulin used be- fore meals in patients with type 1 diabe- tes was shown to be noninferior when compared with aspart insulin for A1C low- ering, with less hypoglycemia observed with inhaled insulin therapy (21). How- ever, the mean reduction in A1C was greater with aspart (–0.21% vs. –0.40%, satisfying the noninferiority margin of 0.4%), and more patients in the insulin aspart group achieved A1C goals of #7.0% (53 mmol/mol) and #6.5% (48 mmol/mol). Because inhaled insulin car- tridges are only available in 4-, 8-, and 12-unit doses, limited dosing increments to fine-tune prandial insulin doses in type 1 diabetes are a potential limitation.

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Investigational Agents
Metformin
Adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in patients with type 1 diabetes. In one study, metformin was found to reduce insulin requirements (6.6 units/day, P , 0.001), and led to small reductions in weight and total and LDL cholesterol but not to improved gly- cemic control (absolute A1C reduction 0.11%, P 5 0.42) (22). A randomized clin- ical trial similarly found that, among over- weight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control and in- creased risk for gastrointestinal adverse events after 6 months compared with placebo (23). The Reducing With Metformin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL) trial investigated the addition of metformin therapy to titrated insulin therapy in adults with type 1 diabetes at increased risk for cardiovascular disease and found that metformin did not signifi- cantly improve glycemic control beyond the first 3 months of treatment and that progression of atherosclerosis (measured by carotid artery intima-media thickness) was not significantly reduced, although other cardiovascular risk factors such as body weight and LDL cholesterol im- proved (24). Metformin is not FDA- approved for use in patients with type 1 diabetes.