Type 1 Diabetes

Treatment Guideline

Prevention ..................................................................................................................................................... 2 Screening Recommendations and Tests ...................................................................................................... 2 Diagnosis....................................................................................................................................................... 2 Treatment ...................................................................................................................................................... 3 Goals ......................................................................................................................................................... 3 Lifestyle modifications and non-pharmacologic options ........................................................................... 3 Blood glucose controlpharmacologic options ........................................................................................ 4 ASCVD prevention .................................................................................................................................... 5 Comorbidity treatment............................................................................................................................... 5 Follow-up/Monitoring..................................................................................................................................... 7 Periodic monitoring of conditions and complications ................................................................................ 7 Recommended comorbidity screening...................................................................................................... 8 Recommended immunizations.................................................................................................................. 8 Evidence Summary ....................................................................................................................................... 9 References .................................................................................................................................................. 11 Clinician Lead and Guideline Development ................................................................................................ 12 Appendix 1. Recommendation Grade Labels ............................................................................................. 13

Most recent comprehensive literature review: May 2012

Guidelines are systematically developed statements to assist patients and providers in choosing appropriate health care for specific clinical conditions. While guidelines are useful aids to assist providers in determining appropriate practices for many patients with specific clinical problems or prevention issues, guidelines are not meant to replace the clinical judgment of the individual provider or establish a standard of care. The recommendations contained in the guidelines may not be appropriate for use in all circumstances. The inclusion of a recommendation in a guideline does not imply coverage. A decision to adopt any particular recommendation must be made by the provider in light of the circumstances presented by the individual patient.

Type 1 Diabetes Treatment Guideline Copyright 19962012 Group Health Cooperative. All rights reserved.

Prevention
While it is possible to identify patients who are at increased risk of developing type 1 diabetes through autoantibody and genetic testing, this is currently being done in research settings. There is no evidencebased strategy for preventing type 1 diabetes.

Screening Recommendations and Tests

Due to low population prevalence, screening for type 1 diabetes is not recommended.

Diagnosis
Table 1. Recommendations for diagnosing diabetes Diagnosis requires abnormal test results on 2 separate days. The results can be from different tests (e.g., one abnormal result from HbA1c and one abnormal fasting plasma glucose). Test HbA1c Results 6.5% or higher on 2 separate days Lower than 6.5% Random plasma glucose 200 mg/dL or higher on 2 separate days Lower than 200 mg/dL Fasting plasma glucose 126 mg/dL or higher on 2 separate days Lower than 100 mg/dL Interpretation Diabetes Normal Diabetes Normal Diabetes Normal

Consider glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) testing for the following patient populations: Younger patients (teenagers) to distinguish early type 1 diabetes from type 2 diabetes. Older adults who are not overweight who are not responding well to oral hypoglycemic and lifestyle (diet/exercise) modification. Table 2. Additional tests to consider for diagnosing type 1 diabetes The GADA and ICA tests should always be performed together. Test Glutamic acid decarboxylase antibody (GADA) Islet cell antibody (ICA) Results Positive Interpretation More than 90% of patients who present with type 1 diabetes will be positive for one or both of these autoantibodies.

The following laboratory tests are not recommended: Fasting C-peptide is not recommended because the test cannot distinguish well between people without diabetes and those with impaired endogenous insulin secretion. C-peptide is released from a person's pancreas in equimolar amounts to endogenous insulin. Because the amount of endogenous insulin secreted is dependent on a patient's blood glucose level, low or undetectable C-peptide levels may indicate either an inability to produce insulin or an absence of insulin secretion due to low blood sugar levels. In the latter case, a person without diabetes would not secrete much C-peptide and would have an abnormal test result. Plasma insulin is not recommended as it does not add any additional useful information.

Type 1 Diabetes Treatment Guideline

Treatment
Goals
Cardiac risk reduction is the most important management issue for patients with diabetes. Table 3. Selected cardiac risk factors and goals for risk reduction Risk factor Blood pressure LDL cholesterol Hemoglobin A1c (HbA1c) Fasting blood glucose
1

Goal Lower than 140/801 mm Hg Lower than 100 mg/dL Lower than 7%2 80120 mg/dL

For patients with diabetes, there are two HEDIS goalslower than 140/90 and lower than 140/80. The Group Health guideline goal was changed to align with the lower HEDIS goal. Certain patientssuch as younger patients and those with microalbuminuriamay benefit from achieving even lower blood pressure levels (e.g., lower than 130/80). While a target HbA1c of lower than 7% is ideal, it may not be achievable for all patients. Any progress should be encouraged. For frail elderly patients, a target HbA1c of 79% is reasonable.

Table 4. Ideal glucose targets Timing Before meals 1 hour post-meals Bedtime 3 a.m. Target 70120 mg/dL 180 mg/dL 70120 mg/dL 70120 mg/dL

Lifestyle modifications and non-pharmacologic options

Diet and physical activity
All patients should strive to: Make smart choices from every food group to meet their caloric needs. Get the most and best nutrition from the calories consumed. Find a balance between food intake and physical activity. Get at least 30 minutes of moderate-intensity physical activity on most days. For personalized eating plans and interactive tools to help patients plan and assess food choices, see the U.S. Department of Agricultures Choose My Plate website (http://www.choosemyplate.gov/). For patients who have been inactive, recommend slowly working up to at least 30 minutes of moderate physical activity per day. If they are unable to be active for 30 minutes at one time, suggest accumulating activity in 10- to 15-minute sessions throughout the day.

Weight management
The risk of serious health conditionssuch as high blood pressure, heart disease, arthritis, and stroke, as well as diabetesincreases with body mass index (BMI) of 25 or higher. (BMI = weight in kilograms divided by height in meters squared [kg/m2].) Overweight is defined as a BMI of 25 to 29.9, obesity as a BMI of 30 or higher. While most overweight or obese adults can lose weight by eating a healthy diet or increasing physical activity, doing both is most effective. See the Group Health Weight Management Guideline for recommendations and further information.
Type 1 Diabetes Treatment Guideline 3

Foot care
For patients at very high risk or increased risk of developing foot ulcers, recommend using a foot skincare kit (https://provider.ghc.org/open/caringForOurMembers/patientHealthEducation/conditionsDiseases/diabete s/footCare.pdf). Foot-ulcer risk definitions: Patients at very high risk are those with a previous foot ulcer, amputation, or major foot deformity (claw/hammer toes, bony prominence, or Charcot deformity). Patients at increased risk are those who are insensate to 5.07 monofilament at any site on either foot or who have bunions, excessive corns, or callus. Patients at average risk are those with none of the aforementioned complications. Encourage patients to check their feet regularly and follow a self-management care agreement. If the patient or a family member cannot perform the patients foot care, encourage the patient to find someone who can provide assistance.

Blood glucose controlpharmacologic options

The long-term goal of insulin treatment is to prevent complications by maintaining blood glucose levels as close to normal as possible. The aggressiveness of therapy should be individualized based on HbA1c goals and the patients ability to engage in self-management. Selected populations may have better clinical results with less aggressive regimens (e.g., very young children, older adults, people with a history of severe hypoglycemia, and those with limited life expectancies or comorbid conditions).

Simple insulin schedules

Table 5. Recommended simple insulin schedules Pre-breakfast (fasting) Once-daily schedules Glargine1 (100%) N/A Glargine1 (50%) or NPH2 (50%) Pre-lunch Pre-dinner Pre-bed

N/A Glargine1 (100%) Glargine1 (50%) or NPH2 (50%)

Twice-daily schedule
1 2

Prior Authorization (PA) for glargine is not required for patients with type 1 diabetes but is required for those with type 2 diabetes. While NPH twice a day is reasonable (and less expensive) for some patients with type 1 diabetes, glargine is associated with lower HbA1c and less hypoglycemia.

Intensive insulin schedules

Patients who are able to engage in the following self-management activities may be good candidates for intensive insulin regimens: Monitoring blood sugar before breakfast (fasting), before lunch, before dinner, and before bed to identify a pattern. Counting and recording carbohydrates. Recalling and recording possible influencing factors for specific blood glucose readings. Adjusting insulin doses in response to given glucose patterns. Coordinating attention to diet, exercise, and insulin therapy. Responding appropriately to hypoglycemia.
Type 1 Diabetes Treatment Guideline 4

Note that blood glucose patterns should be reviewed by the patient every 37 days and adjusted as needed. Insulin doses of greater than 50 units should be split into two separate injections, given in different sites.

Insulin adjustments in response to planned variations in eating or exercise patterns

DietCalculate the carbohydrate content of the meal, and adjust the insulin dose (up or down) 1 unit of insulin for each 15 g of carbohydrate by which the meal varies from a typical meal. (The actual ratio of insulin units to grams of carbohydrate may vary in individuals from 1 unit/5 g of carbohydrate to 1 unit/20 g of carbohydrate.) ExerciseInsulin requirements may change by up to 50% during periods of exercise. Patients should monitor their glucose level every 30 minutes during periods of exercise to determine the effects of exercise on their glucose level. If the effects of the exercise are predictable, insulin doses can be adjusted. Note that stress (due to physical injury, fighting infection or illness, iatrogenic use of steroids, or psychological factors) causes an increase in hormones that antagonize insulin (and thus increases blood glucose unless adjustments are made). Although stress usually causes blood glucose to rise, some people become more agitated and active during stress, leading to a drop in blood glucose.

Continuous subcutaneous insulin infusion (insulin pumps)

Motivated patients with type 1 diabetes for more than 1 year who are having difficulty controlling their blood glucose with conventional intensive insulin regimens may be considered for insulin pumps. For more information within Group Health, see Pharmacys Insulin Pump Handbook.

Continuous glucose monitoring (CGM) systems

Although several FDA-approved CGM systems are available, evidence from randomized controlled trials has not shown significant benefit except in specific situations, such as patients with type 1 diabetes who have well documented frequent and/or severe hypoglycemia (blood glucose under 50 and/or patient has hypoglycemia unawareness) despite best-practice management. For more information, see the clinical review criteria for continuous glucose monitoring (http://www.ghc.org/allsites/clinical/criteria/pdf/continuous_glucose_monitor.pdf).

Options that are not recommended

The following pharmacologic options are not recommended or not on the Group Health formulary; consider consultation with a diabetes expert: Amylin hormonepramlinitide (Symlin) Insulin analoginsulin detemir (Levimir) (PA for children)

ASCVD prevention
Risk-reduction measures to consider include smoking cessation, blood pressure control, statin therapy, ACE inhibitor or angiotensin receptor blocker (ARB) therapy, and antiplatelet therapy. See the Group Health Cardiovascular Disease (ASCVD) Guideline for details.

Comorbidity treatment
Hypertension management
First-line treatment for patients with diabetes and hypertension is an ACE inhibitor or an ARB. See the Group Health Hypertension Guideline for details.

Type 1 Diabetes Treatment Guideline

Sick-day management
Patients experiencing acute illnesses need to be extra vigilant about blood glucose monitoring and control. Within Group Health, the following information and help is available: The Pharmacy's It's Flu Season! Timely Reminders About Diabetes and Sick Day Care contains information about the Sick Day Kit, which is available to patients. The pamphlet Living Well with Type 1 Diabetes: Taking Care of Yourself When Youre Sick" (#337) can be ordered from the Group Health Resource Line (or use SmartPhrase .chronicdiseasedmtype1sickdayplan). Group Health pharmacy staff can help with selecting sugar-free cold medicines and cough syrups.

Type 1 Diabetes Treatment Guideline

Follow-up/Monitoring
Periodic monitoring of conditions and complications
Table 6. Recommended periodic monitoring of conditions and complications Condition/complication Hypertension Blood glucose control Test(s) BP taken with appropriate size cuff using optimal technique HbA1c Frequency Every visit Every 3 months until the target level is reached; thereafter, patient should be monitored every 6 months. Patients at very high risk2 should be seen every 3 months by a wound care nurse. Patients at increased risk2 and average risk2 should be screened annually. Annually Annually Patients with evidence of retinopathy should be screened annually. Grade A Patients without evidence of retinopathy should be screened every 2 years.3 Grade A At least annually

Foot ulcers

Physical exam focused on ankle reflexes, dorsalis pedis pulse, vibratory sensation, and 5.07 monofilament touch sensation performed by a provider qualified to determine the level of risk for foot ulcers Spot urine (microalbuminuria: creatinine ratio)1 Fasting LDL Dilated eye exam by a trained eye services professional or Non-dilated digital photography followed by a comprehensive exam for those who test positive

Microalbuminuria Hyperlipidemia Retinopathy

Electrolyte and chemistry abnormalities

1

Serum creatinine and Serum potassium

The spot urine test (microalbuminuria/creatinine ratio) can identify patients with microalbuminuria by giving a quantitative estimate of protein loss that correlates with 24-hour urinary protein measurements. Test results are expressed in micrograms of urinary albumin per milligram of urinary creatinine (or A:C ratio). Group Health defines a positive test as more than 50 mcg/mg. Although the conventional definition of microalbuminuria is more than 30 mcg/mg, using more than 50 mcg/mg minimizes the number of falsepositive results. Two positive (more than 50 mcg/mg) spot urine tests are diagnostic for microalbuminuria. See Foot care in the Lifestyle modifications and non-pharmacologic options section for foot-ulcer risk definitions. Annual screening is not recommended because the benefits of more frequent screening are marginal: For every 1,000 persons screened annually (instead of every second year), one additional case of proliferative diabetic retinopathy and one additional case of clinically significant macular edema will be detected.

Type 1 Diabetes Treatment Guideline

Recommended comorbidity screening

Screen for depression by using the Patient Health Questionnaire (PHQ-9). Evidence suggests that patients with depression are less likely to be adherent to recommended management plans and less likely to be effective at self-management of diabetes. See the Group Health Adult Depression Guideline or Adolescent Depression Guideline for additional guidance. Patients with major depression can be treated in primary care or offered a referral to Behavioral Health Services for counseling and/or drug therapy.

Recommended immunizations
Table 7. Recommended immunizations for patients with diabetes1 Immunization Influenza Pneumococcal (PPV23) Hepatitis B2
1

Frequency Annually, as early as possible when vaccine becomes available Once between 19 and 64 years Booster after 65 years (5-year minimal interval) Three-dose series for 19 to 59 yrs 60 years and older, depending on risk

See the CDCs Recommended Adult Immunization Schedule for more detailed information (http://www.cdc.gov/vaccines/recs/schedules/downloads/adult/adult-schedule.pdf). Results from observational studies suggest that patients with diabetes are at higher risk for hepatitis B compared to patients without diabetes (CDC 2011).

Type 1 Diabetes Treatment Guideline

Evidence Summary
Diagnosis
Use of HbA1c to diagnose diabetes
A cross-sectional study compared HbA1c of 6.5% or higher and fasting plasma glucose (FPG) of 126 mg/dL or higher for the identification of undiagnosed diabetes among National Health and Nutrition Examination Survey (NHANES) participants. When using HbA1c of 6.5% or higher and FPG of 126 mg/dL or higher as the cut-points for diabetes, results showed that there is moderate agreement between the two tests for the diagnosis of diabetes. Diabetes classification was consistent for the majority of the subjects, with 95.9% being classified as positive by both tests and 1.8% being classified as negative by both tests. Only 0.5% of subjects were classified as positive by one test and negative by the other (Carson 2010).

Treatment
Blood glucose controlpharmacologic options
Rapidly acting insulin analogs versus regular insulin A Cochrane Library meta-analysis of RCTs published through September 2005 found a statistically significant reduction of HbA1c with short-acting insulin analogs compared to regular human insulin for patients with type 1 diabetes (Siebenhofer 2006). However, the difference in HbA1c was small and may not be clinically significant (weighted mean difference = -0.1% [-0.2% to -0.1%]). There was no statistically significant difference in hypoglycemic episodes for patients with type 1 diabetes. The meta-analysis was limited by the overall low quality and short duration of the RCTs. Insulin detemir A recent meta-analysis of RCTs compared insulin detemir to NPH insulin in people with type 1 diabetes and found no significant difference in HbA1c levels; however, a slight reduction was found in the risk of severe and nocturnal hypoglycemia in favor of insulin detemir. There was no data available regarding the long-term safety of insulin detemir (Singh 2009). Continuous glucose monitoring systems Results from a recent meta-analysis that included 22 RCTs and evaluated the effects of continuous glucose monitoring (CGM) compared to self-blood glucose monitoring (SBGM) found that there was limited evidence on the efficacy of CGM in children, adolescents, and adults with type 1 diabetes. The mean difference in HbA1c using real-time CGM compared to SBGM was -0.2% after 6 months of follow-up (Langendam 2012). A recent RCT assessed the benefits of CGM with SMBG compared to SMBG alone in 146 children aged 49 with type 1 diabetes. The mean change in HbA1c was -0.1% in both groups. Results from this study suggest that CGM does not reduce HbA1c in children aged 49 (Mauras 2012).

Follow-up/monitoring
Microalbuminuria
There is no direct evidence from randomized or non-randomized controlled screening trials that microalbuminuria screening improves health outcomes. The recommendation for microalbuminuria screening is based on indirect evidence that the natural history of diabetic renal disease is well known, that screening can identify early disease, and that treatment of patients with microalbuminuria has been shown to improve health outcomes.

Neuropathy
There is fair evidence that diabetic foot screening prevents adverse outcomes. One RCT (McCabe 1998) reported outcomes in patients with diabetes assigned to a foot screening and protection program versus
Type 1 Diabetes Treatment Guideline 9

outcomes in those receiving usual care. At the end of 2 years, there were significantly fewer amputations in the foot-screening group, but no significant difference in the incidence of ulcers. The number needed to screen (NNS) to prevent one amputation = 63 and to prevent one major amputation = 91. No RCTs attempting to replicate these findings were identified.

Retinopathy
There is no direct evidence from randomized or non-randomized controlled screening trials that retinal screening improves health outcomes. The recommendation for retinal screening is based on indirect evidence: namely, that the natural history of diabetic retinal disease is well known, that screening can identify early disease, and that treatments such as blood glucose control and laser therapy have been shown to improve health outcomes. A cohort study investigated the optimum screening interval by grade of retinopathy and found that for patients at low risk for retinopathy, a 2-year screening interval was not associated with increased risk (Misra 2009). Non-mydriatic digital stereoscopic retinal imaging A recent meta-analysis that included 20 observational studies and 4,059 patients examined how mydriasis influenced the accuracy of screening for diabetic retinopathy. Findings from this analysis suggest that mydriatic status alone did not significantly influence the sensitivity or specificity to detect any diabetic retinopathy (Bragge 2011). Results from an observational study that examined the sensitivity and specificity of non-mydriatic digital stereoscopic retinal imaging (NMDSRI) compared to dilated retinal examination performed by an ophthalmologist or an optometrist found that NMDSRI has a sensitivity of 98% and a specificity of 100% for retinopathy within one grade of that indicated by dilated retinal exam (Ahmed 2006). These findings were supported by the results of several other observational studies (Aptel 2008, Boucher 2003, Lin 2002, Vujosevic 2009).

Type 1 Diabetes Treatment Guideline

10

References
Ahmed J, Ward TP, Bursell SE, Aiello LM, Cavallerano JD, Vigersky RA. The sensitivity and specificity of nonmydriatic digital stereoscopic retinal imaging in detecting diabetic retinopathy. Diabetes Care. 2006;29(10):22052209. Aptel F, Denis P, Rouberol F, Thivolet C. Screening of diabetic retinopathy: effect of field number and mydriasis on sensitivity and specificity of digital fundus photography. Diabetes Metab. 2008;34(3):290-293. Boucher MC, Gresset JA, Angioi K, Olivier S. Effectiveness and safety of screening for diabetic retinopathy with two nonmydriatic digital images compared with the seven standard stereoscopic photographic fields. Can J Ophthalmol. 2003;38(7):557-568. Bragge P, Gruen RL, Chau M, Forbes A, Taylor HR. Screening for presence or absence of diabetic retinopathy: a meta-analysis. Arch Ophthalmol. 2011;129(4):435-444. Carson AP, Reynolds K, Fonseca VA, Muntner P. Comparison of A1c and fasting glucose criteria to diagnose diabetes among U.S. adults. Diabetes Care. 2010;33(1):95-97. Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60(50):1709-1711. Langendam MW, Luijf YM, Hooft L, Devries JH, Mudde AH, Scholten RJ. Continuous glucose monitoring systems for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2012;1:CD008101. Lin DY, Blumenkranz MS, Brothers RJ, Grosvenor DM. The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: a comparison with ophthalmoscopy and standardized mydriatic color photography. Am J Ophthalmol. 2002;134(2):204213. Mauras N, Beck R, Xing D, et al. A randomized clinical trial to assess the efficacy and safety of real-time continuous glucose monitoring in the management of type 1 diabetes in young children aged 4 to <10 years. Diabetes Care. 2012;35(2):204-210. McCabe CJ, Stevenson RC, Dolan AM. Evaluation of a diabetic foot screening and protection programme. Diabet Med. 1998;15(1):80-84. Misra A, Bachmann MO, Greenwood RH, et al. Trends in yield and effects of screening intervals during 17 years of a large UK community-based diabetic retinopathy screening programme. Diabet Med. 2009;26(10):1040-1047 Siebenhofer A, Plank J, Berghold A, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev. 2006;(2):CD003287. Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ. 2009;180(4):385-397. Vujosevic S, Benetti E, Massignan F, et al. Screening for diabetic retinopathy: 1 and 3 nonmydriatic 45-degree digital fundus photographs vs 7 standard early treatment diabetic retinopathy study fields. Am J Ophthalmol. 2009;148(1):111-118.

Type 1 Diabetes Treatment Guideline

11

Clinician Lead and Guideline Development

Clinician lead David K. McCulloch, MD, Medical Director, Clinical Improvement Medical Director, Clinical Improvement Phone: 206-326-3938 Most recent comprehensive literature review May 2012 Process of development This evidence-based guideline was developed using an explicit evidence-based process, including systematic literature search, critical appraisal with evidence grading, and evidence synthesis. The following specialties were represented on the development and/or update teams: family medicine, nursing, and pharmacy.

Type 1 Diabetes Treatment Guideline

12

Appendix 1. Recommendation Grade Labels

About the labeling system
This labeling system is adapted from the U.S. Preventive Services Task Force (USPSTF). The label is based on the degree to which the evidence supports the specific clinical recommendation as written by the Group Health guideline team. In this system, certainty refers to the likelihood that the guideline teams assessment of net benefit (i.e., the benefit minus harm of the service as implemented in a general primary care population) is correct, based on the nature of the overall evidence available. While the grades are useful tools in assessing recommendations, they are not meant to replace the clinical judgment of the individual provider or to establish a standard of care.

Recommendation grade definitions

Label Grade A Grade B Grade C Definition The service is recommended. There is high certainty that the net benefit (i.e., benefits minus harms) is substantial. The service is recommended. There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial. The recommendation is against routinely providing the service. There may be considerations that support providing the service to an individual patient. There is at least moderate certainty that the net benefit is small. The recommendation is against providing the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. The current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms. Expert opinion refers to the collective opinion of the Group Health guideline team. The language of the recommendation is at the team's discretion. The evidence is assumed to be insufficient unless otherwise stated. In the rare case there is fair or good evidence, the evidence does not support the expert opinion recommendation put forth by the team.

Grade D I statement

Expert opinion

Levels of certainty regarding net benefit

Level of certainty High Description The available evidence usually includes consistent results from well-designed, wellconducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies. The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by such factors as: The number, size, or quality of individual studies Inconsistency of findings across individual studies Limited generalizability of findings to routine primary care practice Lack of coherence in the chain of evidence As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion. The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of: The limited number or size of studies Important flaws in study design or methods Inconsistency of findings across individual studies Gaps in the chain of evidence Findings that are not generalizable to routine primary care practice A lack of information on important health outcomes More information may allow an estimation of effects on health outcomes.

Moderate

Low

Type 1 Diabetes Treatment Guideline

13