Original Article Annals of Clinical Biochemistry 2015, Vol. 52(1) 76–81 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0004563214522984 acb.sagepub.com
Metformin decreases glycated albumin to glycated haemoglobin ratio in patients with newly diagnosed type 2 diabetes Satoru Sumitani1,2, Shinya Morita2, Reiko Deguchi2, Koichi Hirai2, Kosuke Mukai2, Yoshihiko Utsu2, Shunji Miki2, Bunzo Sato2, Hideji Nakamura1, Soji Kasayama2 and Masafumi Koga3
Abstract Background: To know whether metformin improves postprandial hyperglycaemia, we examined the effect of metformin on the glycated albumin (GA) to glycated haemoglobin (HbA1c) ratio (GA/HbA1c ratio) in patients with newly diagnosed type 2 diabetes. Methods: Metformin and lifestyle interventions were initiated in 18 patients with newly diagnosed type 2 diabetes. Metformin was titrated to 1500 mg/day or maximum-tolerated dose. HbA1c and GA were measured every four weeks up to 24 weeks. Results: HbA1c decreased significantly from 9.0 2.1% at baseline to 6.5 0.9% at week 24, and GA decreased significantly from 24.3 8.2% to 16.2 3.1%. The GA/HbA1c ratio decreased significantly from 2.66 0.37 at baseline to 2.47 0.29 at week 24 (P < 0.01), despite that the GA/HbA1c ratio reached a plateau value at week 16. The change in the GA/HbA1c ratio during 24 weeks (GA/HbA1c ratio) was significantly correlated with both baseline HbA1c and GA. Moreover, the GA/HbA1c ratio was significantly correlated with the change in GA during 24 weeks but not with the change in HbA1c. Conclusions: Metformin decreased the GA/HbA1c ratio in patients with newly diagnosed type 2 diabetes. This suggests that metformin improves postprandial hyperglycaemia in patients with newly diagnosed type 2 diabetes.
Keywords Glycated haemoglobin, glycated albumin, metformin, type 2 diabetes, postprandial hyperglycaemia Accepted: 16th January 2014
Introduction Early and aggressive control to achieve near-normal glycaemia is important to prevent chronic vascular complications in patients with type 2 diabetes. The United Kingdom Prospective Diabetes Study 34 showed that metformin reduces the risk of diabetesrelated endpoints, myocardial infarction, diabetesrelated death and all-cause mortality in patients with
1
Center for Preventive Medicine, Nissay Hospital, Osaka, Japan Department of Medicine, Nissay Hospital, Osaka, Japan 3 Department of Internal Medicine, Kawanishi City Hospital, Kawanishi, Japan 2
Corresponding author: Satoru Sumitani, Center for Preventive Medicine, Nissay Hospital, 6-3-8 Itachibori, Nishi-ku, Osaka 550-0012, Japan. Email: [email protected]
Sumitani et al. newly diagnosed type 2 diabetes.1 However, the mechanisms by which metformin reduces cardiovascular events in patients with type 2 diabetes are still not entirely clear. Recent epidemiological studies suggest that postprandial hyperglycaemia may be an independent risk factor of cardiovascular disease beyond and more powerful than fasting hyperglycaemia.2 Although previous studies have suggested that metformin may improve postprandial hyperglycaemia in highly selected patients,3–5 it remains unclear whether metformin improves postprandial hyperglycaemia in patients with newly diagnosed type 2 diabetes in a routine clinical setting. Glycated haemoglobin (HbA1c) is widely used as a marker of glycaemic control over two to three months. On the other hand, glycated albumin (GA) is another marker of glycaemic control for recent one to two weeks. HbA1c mainly reflects mean plasma glucose concentrations, while GA has been shown to reflect postprandial plasma glucose concentrations as well as mean plasma glucose concentrations. Indeed, GA is higher relative to HbA1c in gastrectomized subjects who show postprandial hyperglycaemia.6 Moreover, GA is higher relative to HbA1c due to marked glycaemic excursions in patients with type 1 diabetes than patients with type 2 diabetes7, and in patients with type 2 diabetes treated with insulin than those treated without insulin.8 Continuous glucose monitoring showed that GA is a better maker of glucose excursions than other markers such as HbA1c and 1,5-anhydroglucitol.9 Because GA is higher relative to HbA1c in patients with postprandial hyperglycaemia, the GA to HbA1c ratio (GA/HbA1c ratio) is higher in those patients. In this regard, previous studies have demonstrated that the GA/HbA1c ratio reflects postprandial plasma glucose concentrations.10,11 Thus, administration of a drug that improves postprandial hyperglycaemia might lower the GA/HbA1c ratio. In this study, to investigate whether metformin is effective for decreasing postprandial plasma glucose concentrations, we examined the effect of metformin on the GA/HbA1c ratio in patients with newly diagnosed type 2 diabetes.
Material and methods Study design and patients This is a subanalysis of the effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with newly diagnosed type 2 diabetes (EMINENT) study, which was a prospective observational study within a routine clinical setting to examine the effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with
77 newly diagnosed type 2 diabetes. The details of the EMINENT study were described elsewhere.12 Briefly, eligible patients were newly diagnosed patients with type 2 diabetes aged 20–75 years with HbA1c concentrations 56.5% and who had never taken oral hypoglycaemic agents. The diagnosis of type 2 diabetes was made on the WHO 1999 criteria.13 We excluded patients with liver cirrhosis, renal disease or anaemia from the study. Metformin and lifestyle interventions were initiated at the time of diagnosis, and the dose of metformin was titrated to 1500 mg/day or maximumtolerated dose. Lifestyle interventions were composed of an individualized dietary counselling and an encouragement to increase daily physical activities. The primary outcomes were reduction in HbA1c and the proportion of patients who achieved HbA1c
Metformin decreases glycated albumin to glycated haemoglobin ratio in patients with newly diagnosed type 2 diabetes Satoru Sumitani1,2, Shinya Morita2, Reiko Deguchi2, Koichi Hirai2, Kosuke Mukai2, Yoshihiko Utsu2, Shunji Miki2, Bunzo Sato2, Hideji Nakamura1, Soji Kasayama2 and Masafumi Koga3
Abstract Background: To know whether metformin improves postprandial hyperglycaemia, we examined the effect of metformin on the glycated albumin (GA) to glycated haemoglobin (HbA1c) ratio (GA/HbA1c ratio) in patients with newly diagnosed type 2 diabetes. Methods: Metformin and lifestyle interventions were initiated in 18 patients with newly diagnosed type 2 diabetes. Metformin was titrated to 1500 mg/day or maximum-tolerated dose. HbA1c and GA were measured every four weeks up to 24 weeks. Results: HbA1c decreased significantly from 9.0 2.1% at baseline to 6.5 0.9% at week 24, and GA decreased significantly from 24.3 8.2% to 16.2 3.1%. The GA/HbA1c ratio decreased significantly from 2.66 0.37 at baseline to 2.47 0.29 at week 24 (P < 0.01), despite that the GA/HbA1c ratio reached a plateau value at week 16. The change in the GA/HbA1c ratio during 24 weeks (GA/HbA1c ratio) was significantly correlated with both baseline HbA1c and GA. Moreover, the GA/HbA1c ratio was significantly correlated with the change in GA during 24 weeks but not with the change in HbA1c. Conclusions: Metformin decreased the GA/HbA1c ratio in patients with newly diagnosed type 2 diabetes. This suggests that metformin improves postprandial hyperglycaemia in patients with newly diagnosed type 2 diabetes.
Keywords Glycated haemoglobin, glycated albumin, metformin, type 2 diabetes, postprandial hyperglycaemia Accepted: 16th January 2014
Introduction Early and aggressive control to achieve near-normal glycaemia is important to prevent chronic vascular complications in patients with type 2 diabetes. The United Kingdom Prospective Diabetes Study 34 showed that metformin reduces the risk of diabetesrelated endpoints, myocardial infarction, diabetesrelated death and all-cause mortality in patients with
1
Center for Preventive Medicine, Nissay Hospital, Osaka, Japan Department of Medicine, Nissay Hospital, Osaka, Japan 3 Department of Internal Medicine, Kawanishi City Hospital, Kawanishi, Japan 2
Corresponding author: Satoru Sumitani, Center for Preventive Medicine, Nissay Hospital, 6-3-8 Itachibori, Nishi-ku, Osaka 550-0012, Japan. Email: [email protected]
Sumitani et al. newly diagnosed type 2 diabetes.1 However, the mechanisms by which metformin reduces cardiovascular events in patients with type 2 diabetes are still not entirely clear. Recent epidemiological studies suggest that postprandial hyperglycaemia may be an independent risk factor of cardiovascular disease beyond and more powerful than fasting hyperglycaemia.2 Although previous studies have suggested that metformin may improve postprandial hyperglycaemia in highly selected patients,3–5 it remains unclear whether metformin improves postprandial hyperglycaemia in patients with newly diagnosed type 2 diabetes in a routine clinical setting. Glycated haemoglobin (HbA1c) is widely used as a marker of glycaemic control over two to three months. On the other hand, glycated albumin (GA) is another marker of glycaemic control for recent one to two weeks. HbA1c mainly reflects mean plasma glucose concentrations, while GA has been shown to reflect postprandial plasma glucose concentrations as well as mean plasma glucose concentrations. Indeed, GA is higher relative to HbA1c in gastrectomized subjects who show postprandial hyperglycaemia.6 Moreover, GA is higher relative to HbA1c due to marked glycaemic excursions in patients with type 1 diabetes than patients with type 2 diabetes7, and in patients with type 2 diabetes treated with insulin than those treated without insulin.8 Continuous glucose monitoring showed that GA is a better maker of glucose excursions than other markers such as HbA1c and 1,5-anhydroglucitol.9 Because GA is higher relative to HbA1c in patients with postprandial hyperglycaemia, the GA to HbA1c ratio (GA/HbA1c ratio) is higher in those patients. In this regard, previous studies have demonstrated that the GA/HbA1c ratio reflects postprandial plasma glucose concentrations.10,11 Thus, administration of a drug that improves postprandial hyperglycaemia might lower the GA/HbA1c ratio. In this study, to investigate whether metformin is effective for decreasing postprandial plasma glucose concentrations, we examined the effect of metformin on the GA/HbA1c ratio in patients with newly diagnosed type 2 diabetes.
Material and methods Study design and patients This is a subanalysis of the effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with newly diagnosed type 2 diabetes (EMINENT) study, which was a prospective observational study within a routine clinical setting to examine the effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with
77 newly diagnosed type 2 diabetes. The details of the EMINENT study were described elsewhere.12 Briefly, eligible patients were newly diagnosed patients with type 2 diabetes aged 20–75 years with HbA1c concentrations 56.5% and who had never taken oral hypoglycaemic agents. The diagnosis of type 2 diabetes was made on the WHO 1999 criteria.13 We excluded patients with liver cirrhosis, renal disease or anaemia from the study. Metformin and lifestyle interventions were initiated at the time of diagnosis, and the dose of metformin was titrated to 1500 mg/day or maximumtolerated dose. Lifestyle interventions were composed of an individualized dietary counselling and an encouragement to increase daily physical activities. The primary outcomes were reduction in HbA1c and the proportion of patients who achieved HbA1c
