PRE -ASSESSMENT Diabetic Testing Before CCOHTA decides to undertake a health technology assessment, a pre-assessment of the literature is performed. Pre-assessments are based on a limited literature search; they are not CCOHTA extensive, systematic reviews of the literature. They are provided here as a quick guide to important, No. 34 current assessment information on this topic. Readers are cautioned that the pre-assessments have May 2004 not been externally peer reviewed. Introduction Diabetes is prevalent in 5% of the Canadian population.1 Type 2 non-insulin dependent diabetes mellitus (NIDDM) accounts for 85% to 90% of patients with diabetes mellitus. Patients with diabetes have an increased risk for developing complications from cardiovascular (i.e., heart, cerebrovascular and peripheral vascular) disease including neuropathy (leading to limb amputation), retinopathy (leading to blindness) and nephropathy (leading to dialysis and transplant). The clinical management of diabetes ranges from surveillance and primary prevention (preventing disease occurrence) to secondary prevention and management of complications. Regular treatment and the measurement of blood lipid parameters, blood pressure and glycemia used to modify treatment plans are encouraged in patients with type 1 (insulin-dependent) or type 2 diabetes (Figure 1).1 Figure 1: Diagnosis and care of diabetes based on glycemic control Management of Diabetes Treating:Treating 1. What is the evidence that LifestyleEducation –about physical improved glycemic control nutritional,lifestyle, nutrition and and delays or leads to fewer disease knowledge complications education Diagnosis and and screening screening AntihyperglycemicAntihyperglycemic medications Glycemic Complications Type 1 control Type 1 or death or typetype 2 2 diabetes diabetes Testing:Testing GlucoseFasting in bloodplasma or plasmaglucose Fructosamine 2. What is the evidence that testing leads to HbA 1c improved glycemic control? The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca) PRE-ASSESSMENT Diabetic Testing CCOHTA Tests for glycemia are supposed to help patients maintain glycemic control. These tests include fasting blood and plasma glucose measurements, glycosylated hemoglobin measurements (HbA1c) and fructosamine measurements. Traditionally, HbA1c tests are done in a laboratory and blood glucose tests at home. Point-of-care and home-based tests have been developed for HbA1c and fructosamine testing. At issue is the scientific evidence supporting glucose testing in diabetes. The necessary minimum condition for any test is that its output may cause a change in a patient’s clinical management. The test results must also decrease the probability of disease once a new 2 treatment plan is chosen. Research Questions Based on the current recommendations for the diagnosis and management of diabetes: 1) What is the scientific evidence that tests of glycemia lead to reduced or delayed complications in patients diagnosed with type 1 or type 2 diabetes? If there is evidence that testing of glycemia leads to reduced or delayed complications, what is the optimal frequency of testing? 2 a) What is the scientific evidence that testing leads to improved glycemic control? In particular, what is the evidence that self-monitoring of blood glucose (SMBG), point-of-care or self-monitoring of glycosylated hemoglobin or fructosamine monitoring in any setting will lead to better glycemic control? b) If there is evidence that testing leads to improved glycemic control, what is the optimal frequency? c) What is the evidence that testing results are used to modify lifestyle and medication therapy for persons with diabetes? 3) What is the evidence that improving glycemic control leads to reduced or delayed complications in individuals diagnosed with type 1 or type 2 diabetes? Assessment Process Literature was identified by searching MEDLINE® via PubMed (1966-11 Aug 2003), The Cochrane Library (2003 Issue 3), web sites, clinical practice guidelines and clinical trial registries, according to the Canadian Coordinating Office for Health Technology Assessment’s (HTA) checklist. The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca) PRE-ASSESSMENT Diabetic Testing CCOHTA Summary of Findings Approximately 1,500 citations were captured during the electronic search. Citations describing research that focuses on the relevant clinical questions are listed in Tables 1 and 2. Trials and observational studies were captured in this preliminary search. Research question 1) What is the evidence that testing leads to reduced or delayed complications or death for individuals diagnosed with type 1 or type 2 diabetes? Response to question 1) None of the randomized controlled trials identified compared testing versus no testing and assessed its impact on complications or death. Research question 2 a) What is the evidence that testing leads to improved glycemic control? In particular, what is the evidence that SMBG, point-of-care or self-monitoring of glycosylated hemoglobin or fructosamine monitoring in any setting will lead to better glycemic control? Response to question 2 a) Several reviews, including two systematic reviews of the evidence from RCTs, were found (Table 1). The authors of one systematic review3 conducted a meta-analysis. In children or adult type 1 diabetics, blood glucose monitoring led to a detectable difference in glycosylated hemoglobin (mean difference 0.57%, 95%CI: 1.073 to 0.061) when compared to urine monitoring. On the contrary, no difference between SMBG and urine glucose was detectable from studies involving type 2 diabetics. Further to this, a significant effect on glycemic control from self-monitoring could not be detected. For type 1, we identified one new RCT and eight previously identified RCTs. Three interrupted time-series, five prospective cohort studies, nine retrospective or cross- sectional studies and three surveys were also identified (Table 2). For type 2, two new RCTs were identified (one ongoing), with eight RCTs that were previously identified. Two non-randomized studies, one interrupted time series, two prospective cohort studies, 11 retrospective or cross-sectional cohort studies and four surveys were identified (Table 3). The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca) PRE-ASSESSMENT Diabetic Testing CCOHTA Table 1: Reviews identified for question 2 a) Citation Type of Report (if known) Conclusions (if known) Coster, Gulliford, et al. Systematic review 20003 conducted for NCCHTA/NICE Grimaldi & Sachon Review Prospective randomized studies are needed 20034 to confirm efficiency of SMBG in type 2 diabetes Goldstein, Little, et al. Review and guidance 20035 Court 20026 Unknown Kennedy 20017 Review Unknown Norris, Engelgau, et al. Systematic review of training 20018 (which might include SMBG) Hom 19999 Review Unknown Rindone 199810 Unclear whether this is a review Halimi 199811 Review Use of SMBG is increasingly recommended by diabetologists and general practitioners, but trials investigating effects of SMBG in NIDDM patients found no benefit for metabolic control or weight loss; we recommend a moderate use of SMBG in NIDDM patients Faas, Schellevis, et al. Efficacy of SMBG in NIDDM patients is 199712 questionable and should be tested in rigorous high-quality RCT, for which some recommendations are given Goldstein, Little, et al. Review Unknown 199513 Goldstein 199414 Review Unknown Patrick, Gill, et al. Commentary 199415 Wysocki 198916 Review Blohme 198317 Review The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca) PRE-ASSESSMENT Diabetic Testing CCOHTA SMBG in type 1 diabetes: Our search revealed one new RCT. Most of the studies identified were cross-sectional cohort studies or surveys. One identified RCT evaluated continuous glucose monitoring as an addition to standard monitoring. Several prospective cohorts were identified; two suggested SMBG can lead to tighter glycemic control (Table 2). Table 2: Studies of SMBG in type 1 diabetes Citation Design and Patient Group Results Ludvigsson & Hanas RCT of children (n=27) to HbA1c decreased in unmasked arm 200318 continued glucose monitoring (7.70% to 7.31%) after 3 months but not in blind arm (7.75% to 7.65%) Adams, Mah, et al. Cross-sectional cohort study of Lower rates of SMBG associated with 19 2003 adults (n=4,565) lower HbA1c testing frequency and higher HbA1c levels in insulin-dependent Otieno, Ng'ang'a, et Cross-sectional study (n=?) in Morning random blood glucose within al. 200220 Kenyan ambulatory clinic usual therapeutic targets of 4 mmol/L to 8 mmol/L predicted good glycemic control (HbA1c≤7.8%) with high sensitivity at the range of 86.3% to 98.4% Rotchford & Cross-sectional retrospective Blood glucose monitoring not regularly 21 Rotchford 2002 design (n=253) in South Africa performed and medications rarely modified, mean HbA1c 11.3% Salardi, Zucchini, et Retrospective cohort (n=28) of CGM correlates with HbA1c (r=0.53, al. 200222 CGM users p=0.002) and decreased during OL cohort study Soumerai, Mah, et Quasi-experimental