XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Background HbA1c is a widely used biomarker for diabetes mellitus management. Here, we evaluated the accuracy of six methods for determining HbA1c values in Chinese patients with common α- and β-globin chains variants in China. Methods Blood samples from normal subjects and individuals exhibiting hemoglobin variants were analyzed for HbA1c, using Sebia Capillarys 2 Flex Piercing (C2FP), Bio-Rad Variant II Turbo 2.0, Tosoh HLC-723 G8 (ver. 5.24), Arkray ADAMS A1c HA-8180V fast mode, Cobas c501 and Trinity Ultra2 systems. Results DNA sequencing revealed five common β-globin chain variants and three common α-globin chain variants. The most common variant was Hb E, followed by Hb New York, Hb J-Bangkok, Hb G-Coushatta, Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2 and Hb G-Taipei. Variant II Turbo 2.0, Ultra2 and Cobas c501 showed good agreement with C2FP for most samples with variants. HLC-723 G8 yielded no HbA1c values for Hb J-Bangkok, Hb Q-Thailand and Hb G-Honolulu. Samples with Hb E, Hb G-Coushatta, Hb G-Taipei and Hb Ube-2 produced significant negative biases for HLC-723 G8. HA-8180V showed statistically significant differences for Hb E, Hb G-Coushatta, Hb G-Taipei, Hb Q-Thailand and Hb G-Honolulu. HA-8180V yielded no HbA1c values for Hb J-Bangkok. All methods showed good agreement for samples with Hb New York. Conclusions Some common hemoglobin variants can interfere with HbA1c determination by the most popular methods in China.

Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods

Globally, the incidence of diabetes mellitus is rising at an alarming rate and has become a health crisis that threatens the economies of all nations. Therefore, diagnosing diabetes has become an important issue in the management of diabetes. Glycated hemoglobin (HbA1c) is now recommended as a means to diagnose diabetes, but its use still has limitations. In this article, the biology, measurement, standardization, and opportunities and challenges of the use of HbA1c to diagnose diabetes are reviewed. More specifically, its use in China and the Asian region is discussed in detail.

Standardising HbA1c-based diabetes diagnosis: opportunities and challenges.

Background Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Methods Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Results Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. Conclusions HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

Hb variants in Korea: Effect on HbA1c using five routine methods

Objectives Hemoglobin (Hb) variant is one of the most common monogenic inherited disorders. We aimed to explore the prevalence and hematological and molecular characteristics of Hb variants in southern China. Methods We collected blood samples from all patients with suspected variants found during HbA1c measurement via a cation-exchange high-performance liquid chromatography system (Bio-Rad Variant II Turbo 2.0) or a capillary electrophoresis method (Sebia Capillarys). Hematological analysis, Sanger sequencing, and gap-PCR were performed for these samples. Results Among the 311,024 patients tested, we found 1,074 Hb variant carriers, including 823 identified using Capillarys and 251 using Variant II Turbo 2.0, with a total carrier rate of 0.35%. We discovered 117 types of Hb variants (52 HBB, 47 HBA, and 18 HBD mutations) containing 18 new mutations. The most common variant found was Hb E, followed by Hb New York, Hb J-Bangkok, Hb Q-Thailand, Hb G-Coushatta, Hb G-Honolulu, Hb G-Taipei, and Hb Broomhill. Most heterozygotes for the Hb variant exhibited normal hematological parameters. However, most patients with compound heterozygotes for the Hb variant and thalassemia showed varied degrees of microcytic hypochromic anemia. Conclusions The prevalence of hemoglobin variants remains high and exhibits genetic diversity and widespread distribution in the population of southern China.

Hemoglobin variants in southern China: results obtained during the measurement of glycated hemoglobin in a large population

Background HbA1c is a widely used biomarker for the management of diabetes mellitus and can be quantified from blood samples by using various methods, including ion-exchange high-performance liquid chromatography (HPLC), boronate affinity HPLC, and capillary electrophoresis (CE). Here, we evaluated the accuracy of four separation methods for determination of HbA1c values in Chinese patients with different hemoglobin disorders. Methods Blood samples from normal patients, patients with β-thalassemia, patients exhibiting heterozygosity, and patients exhibiting homozygosity were analyzed using ion-exchange HPLC (Variant II Turbo, Bio-Rad and Adams A1c HA-8160, Arkray, run in diabetes mode), boronate affinity HPLC (Ultra2, Trinity Biotech), and CE (Capillarys 2 Flex Piercing, Sebia). Results Samples from patients with β-thalassemia produced significant positive biases on the Variant II Turbo system compared to the other three systems. For heterozygous βA/βE patients, a good agreement was observed between Capillarys 2 Flex Piercing and Ultra2 systems, while a significant negative bias was observed between HA-8160 and Capillarys 2 Flex Piercing systems and between Variant II Turbo and Capillarys 2 Flex Piercing systems. For homozygous (βE/βE) patients, a clear context without HbA, all systems except the Capillarys 2 Flex Piercing system yielded random HbA1c results. Only the Capillarys 2 Flex Piercing system could detect all hemoglobin variants tested. Conclusions β-Thalassemia can cause errors in HbA1c determination using the Variant II Turbo system. HbE heterozygosity or HbE homozygosity also complicated HbA1c measurements. The Capillarys 2 Flex Piercing system detected all Hb variants and HbA1c in patients with β-thalassemia and could provide measurements with high accuracy.

Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants.

Evaluation of MALDI-TOF MS for the measurement of glycated hemoglobin.

Background

α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus Here, we evaluated the effects of different genotypes α-thalassemia on HbA1c measurement



Methods

A total of 189 samples from nondiabetic patients were analyzed HbA1c analysis was performed by ion-exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis Fasting glucose, fructosamin, and HbA2 were also performed All samples were confirmed by genotyping for thalassemia



Results

In patients with two or three functional α-genes, HbA1c values were not significantly different from those of controls (P > 005); however, in individuals with α-thalassemia with one functional α-gene (ie, HbH disease), HbA1c levels were significantly different from those of controls (P 005)



Conclusions

In this study, HbA1c values in samples from individuals with two or three functional α-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not

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Anping Xu

Papers

Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants.

Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods

Hemoglobin variants in southern China: results obtained during the measurement of glycated hemoglobin in a large population

Evaluation of MALDI-TOF MS for the measurement of glycated hemoglobin.

Effects of α-Thalassemia on HbA1c Measurement.