diabetes research and clinical practice 106 (2014) e41–e43
Contents available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief Report
Vitamin D deficiency is significantly associated with retinopathy in young Japanese type 1 diabetic patients Naoki Shimo a, Tetsuyuki Yasuda a, Hideaki Kaneto a,*, Naoto Katakami a, Akio Kuroda b, Fumie Sakamoto a, Mitsuyoshi Takahara a, Yoko Irie a, Keiko Horikawa a, Kazuyuki Miyashita a, Takeshi Miyatsuka a, Kazutomi Yoshiuchi c, Dan Kawamori a, Ken’ya Sakamoto c, Taka-aki Matsuoka b, Keisuke Kosugi c, Iichiro Shimomura a, Munehide Matsuhisa b a
Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan Clinical Research Center for Diabetes, Tokushima University, Tokushima, Japan c Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan b
article info
abstract
Article history:
The aim of this study was to examine the possible association of vitamin D deficiency with
Received 16 July 2014
diabetic retinopathy in 75 young Japanese type 1 diabetic patients. A multivariate regression
Accepted 5 August 2014
analysis, duration of diabetes and vitamin D deficiency were independent determinants of
Available online 12 August 2014
diabetic retinopathy. # 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Vitamin D deficiency Type 1 diabetes Retinopathy
1.
Introduction
Diabetic retinopathy (DR) is one of the most common complications and is a major cause of acquired blindness in diabetic patients [1]. It is well known that poor glycemic control and duration of diabetes are independent risk factors of DR [2]. However, detailed pathophysiological mechanisms and other risk factors of DR are not fully clarified.
Vitamin D (VD) has been classically known to regulate bone and mineral homeostasis, and its deficiency leads to cause of rickets in children and osteomalacia in adults [3]. However, in addition to its classical role, recent studies have shown nonclassical roles of VD in the pathogenesis of cancer, autoimmune diseases, diabetes, and cardiovascular diseases [4]. Furthermore, experimental animal studies have shown protective effects of VD on DR [5,6]. These results suggest the hypothesis that vitamin D deficiency (VDD) may be
* Corresponding author at: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: +81 6 6879 3743; fax: +81 6 6879 3739. E-mail address: [email protected] (H. Kaneto). http://dx.doi.org/10.1016/j.diabres.2014.08.005 0168-8227/# 2014 Elsevier Ireland Ltd. All rights reserved.
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diabetes research and clinical practice 106 (2014) e41–e43
Table 1 – Clinical characteristics of type 1 diabetic patients with or without VDD.
Sex (male/female) Age (years) Duration of diabetes (years) Smoking (%) BMI (kg/m2) HbA1c (%) Systolic BP (mmHg) Diastolic BP (mmHg) Triglyceride (mg/dL) HDL-C (mg/dL) LDL-C (mg/dL) eGFR (ml/min/1.73 m2) Retinopathy (NDR/SDR) UACR (mg/gCr) 25(OH)D3 (ng/mL)
Patients with VDD (n = 21)
Patients without VDD (n = 54)
6/15 28.7 4.7 20.4 5.9
22/32 28.5 5.8 19.4 6.9
0.33 0.87 0.57
14.3 23.6 3.8 8.2 1.6 116 14 68 10 79 51 69 12 104 29 128 41 8/13
7.4 22.8 2.6 7.6 1.3 118 15 67 10 78 58 70 13 100 21 110 34 36/18
0.18 0.36 0.07 0.53 0.87 0.95 0.81 0.51 0.05 0.02
18.1 34.0 16.7 2.9
15.1 31.0 29.4 7.5
0.78 –
P
Data are means SD. VDD, vitamin D deficiency; BMI, body mass index; BP, blood pressure; HbA1c, glycated hemoglobin A1c; HDLC, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; UACR, urinary albumin to creatinine ratio.
when hyperglycemia and/or ketosis were observed, and all patients were treated with insulin. Patients with pregnancy, hepatic disease and malignancy, and taking medications that affect VD status were excluded from the study. This study was approved by the local ethics committee, and informed consent was obtained from all patients. Blood samples were obtained after 12 h fasting state in summer period. VD status was evaluated by the measurement of serum 25(OH)D3 levels using the RIA (SRL Inc., Tokyo, Japan). VDD was defined as serum 25(OH)D3 level below 20 ng/mL in accordance with the generally accepted standard [7]. Presence of retinopathy was diagnosed by a diabetologist based on the findings of single-field fundus photography, and classified as non-diabetic retinopathy (NDR) and simple or more advanced diabetic retinopathy (SDR). Continuous variables are expressed as means SD. Differences between type 1 diabetic patients with and without retinopathy were examined by the x2 test or unpaired Student’s t-tests as appropriate. A logistic multivariate regression analysis was performed to assess variables significantly associated with diabetic retinopathy. A two-sided value of P < 0.05 was considered statistically significant. Theses statistical analyses were performed using JMP statistical software (SAS Institute, Japan).
3. involved in DR. However, there are few studies evaluating the association of VDD with retinopathy in type 1 diabetic patients. In the present study, we determined serum 25(OH)D3 levels in young onset Japanese type 1 diabetic patients and examined the possible association of VDD with DR.
2.
Patients and methods
We recruited 75 young Japanese type 1 diabetic patients (28.5 5.5 years old) who had annual medical checkups for diabetic complications at the Diabetic Clinic of Osaka University Hospital and the Osaka Police Hospital in summer periods. Type 1 diabetes was diagnosed by diabetologists
Results
Of 75 type 1 diabetic patients, 21 patients (28.0%) had VDD. The clinical and biochemical characteristics in type 1 diabetic patients with or without VDD are shown in Table 1. The prevalence of retinopathy was significantly higher in patients with VDD compared to those without VDD. Other clinical parameters including age, HbA1c, duration of diabetes, smoking, body mass index, blood pressure, and lipid profile were not different between the groups. To assess the specific risk factors significantly associated with DR, a logistic regression analysis was performed (Table 2). In a univariate regression analysis, age, duration of diabetes, and VDD were significantly associated with DR. Furthermore, in a multivariate regression analysis, duration of diabetes
Table 2 – Univariate and multivariate regression analyses of retinopahty in type 1 diabetic patients. Multivariate
Univariate
Age (years) Sex (male) Duration of diabetes (years) Smoking (0 = no, 1 = yes) BMI (kg/m2) HbA1c (%) Triglyceride (mg/dL) HDL-C (mg/dL) LDL-C (mg/dL) eGFR (ml/min/1.73 m2) Log UACR Vitamin D (deficient)
Unadjusted OR
95% CI
P
Adjusted OR
95% CI
P
1.11 2.01 1.14 0.70 1.18 1.28 1.01 1.00 1.00 0.99 1.58 3.25
1.01–1.21 0.78–5.18 1.05–1.24 0.35–1.39 0.99–1.41 0.91–1.80 1.00–1.02 0.97–1.04 0.98–1.02 0.98–1.01 0.99–2.52 1.14–9.26
0.03 0.15
Contents available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief Report
Vitamin D deficiency is significantly associated with retinopathy in young Japanese type 1 diabetic patients Naoki Shimo a, Tetsuyuki Yasuda a, Hideaki Kaneto a,*, Naoto Katakami a, Akio Kuroda b, Fumie Sakamoto a, Mitsuyoshi Takahara a, Yoko Irie a, Keiko Horikawa a, Kazuyuki Miyashita a, Takeshi Miyatsuka a, Kazutomi Yoshiuchi c, Dan Kawamori a, Ken’ya Sakamoto c, Taka-aki Matsuoka b, Keisuke Kosugi c, Iichiro Shimomura a, Munehide Matsuhisa b a
Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan Clinical Research Center for Diabetes, Tokushima University, Tokushima, Japan c Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan b
article info
abstract
Article history:
The aim of this study was to examine the possible association of vitamin D deficiency with
Received 16 July 2014
diabetic retinopathy in 75 young Japanese type 1 diabetic patients. A multivariate regression
Accepted 5 August 2014
analysis, duration of diabetes and vitamin D deficiency were independent determinants of
Available online 12 August 2014
diabetic retinopathy. # 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Vitamin D deficiency Type 1 diabetes Retinopathy
1.
Introduction
Diabetic retinopathy (DR) is one of the most common complications and is a major cause of acquired blindness in diabetic patients [1]. It is well known that poor glycemic control and duration of diabetes are independent risk factors of DR [2]. However, detailed pathophysiological mechanisms and other risk factors of DR are not fully clarified.
Vitamin D (VD) has been classically known to regulate bone and mineral homeostasis, and its deficiency leads to cause of rickets in children and osteomalacia in adults [3]. However, in addition to its classical role, recent studies have shown nonclassical roles of VD in the pathogenesis of cancer, autoimmune diseases, diabetes, and cardiovascular diseases [4]. Furthermore, experimental animal studies have shown protective effects of VD on DR [5,6]. These results suggest the hypothesis that vitamin D deficiency (VDD) may be
* Corresponding author at: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: +81 6 6879 3743; fax: +81 6 6879 3739. E-mail address: [email protected] (H. Kaneto). http://dx.doi.org/10.1016/j.diabres.2014.08.005 0168-8227/# 2014 Elsevier Ireland Ltd. All rights reserved.
e42
diabetes research and clinical practice 106 (2014) e41–e43
Table 1 – Clinical characteristics of type 1 diabetic patients with or without VDD.
Sex (male/female) Age (years) Duration of diabetes (years) Smoking (%) BMI (kg/m2) HbA1c (%) Systolic BP (mmHg) Diastolic BP (mmHg) Triglyceride (mg/dL) HDL-C (mg/dL) LDL-C (mg/dL) eGFR (ml/min/1.73 m2) Retinopathy (NDR/SDR) UACR (mg/gCr) 25(OH)D3 (ng/mL)
Patients with VDD (n = 21)
Patients without VDD (n = 54)
6/15 28.7 4.7 20.4 5.9
22/32 28.5 5.8 19.4 6.9
0.33 0.87 0.57
14.3 23.6 3.8 8.2 1.6 116 14 68 10 79 51 69 12 104 29 128 41 8/13
7.4 22.8 2.6 7.6 1.3 118 15 67 10 78 58 70 13 100 21 110 34 36/18
0.18 0.36 0.07 0.53 0.87 0.95 0.81 0.51 0.05 0.02
18.1 34.0 16.7 2.9
15.1 31.0 29.4 7.5
0.78 –
P
Data are means SD. VDD, vitamin D deficiency; BMI, body mass index; BP, blood pressure; HbA1c, glycated hemoglobin A1c; HDLC, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; UACR, urinary albumin to creatinine ratio.
when hyperglycemia and/or ketosis were observed, and all patients were treated with insulin. Patients with pregnancy, hepatic disease and malignancy, and taking medications that affect VD status were excluded from the study. This study was approved by the local ethics committee, and informed consent was obtained from all patients. Blood samples were obtained after 12 h fasting state in summer period. VD status was evaluated by the measurement of serum 25(OH)D3 levels using the RIA (SRL Inc., Tokyo, Japan). VDD was defined as serum 25(OH)D3 level below 20 ng/mL in accordance with the generally accepted standard [7]. Presence of retinopathy was diagnosed by a diabetologist based on the findings of single-field fundus photography, and classified as non-diabetic retinopathy (NDR) and simple or more advanced diabetic retinopathy (SDR). Continuous variables are expressed as means SD. Differences between type 1 diabetic patients with and without retinopathy were examined by the x2 test or unpaired Student’s t-tests as appropriate. A logistic multivariate regression analysis was performed to assess variables significantly associated with diabetic retinopathy. A two-sided value of P < 0.05 was considered statistically significant. Theses statistical analyses were performed using JMP statistical software (SAS Institute, Japan).
3. involved in DR. However, there are few studies evaluating the association of VDD with retinopathy in type 1 diabetic patients. In the present study, we determined serum 25(OH)D3 levels in young onset Japanese type 1 diabetic patients and examined the possible association of VDD with DR.
2.
Patients and methods
We recruited 75 young Japanese type 1 diabetic patients (28.5 5.5 years old) who had annual medical checkups for diabetic complications at the Diabetic Clinic of Osaka University Hospital and the Osaka Police Hospital in summer periods. Type 1 diabetes was diagnosed by diabetologists
Results
Of 75 type 1 diabetic patients, 21 patients (28.0%) had VDD. The clinical and biochemical characteristics in type 1 diabetic patients with or without VDD are shown in Table 1. The prevalence of retinopathy was significantly higher in patients with VDD compared to those without VDD. Other clinical parameters including age, HbA1c, duration of diabetes, smoking, body mass index, blood pressure, and lipid profile were not different between the groups. To assess the specific risk factors significantly associated with DR, a logistic regression analysis was performed (Table 2). In a univariate regression analysis, age, duration of diabetes, and VDD were significantly associated with DR. Furthermore, in a multivariate regression analysis, duration of diabetes
Table 2 – Univariate and multivariate regression analyses of retinopahty in type 1 diabetic patients. Multivariate
Univariate
Age (years) Sex (male) Duration of diabetes (years) Smoking (0 = no, 1 = yes) BMI (kg/m2) HbA1c (%) Triglyceride (mg/dL) HDL-C (mg/dL) LDL-C (mg/dL) eGFR (ml/min/1.73 m2) Log UACR Vitamin D (deficient)
Unadjusted OR
95% CI
P
Adjusted OR
95% CI
P
1.11 2.01 1.14 0.70 1.18 1.28 1.01 1.00 1.00 0.99 1.58 3.25
1.01–1.21 0.78–5.18 1.05–1.24 0.35–1.39 0.99–1.41 0.91–1.80 1.00–1.02 0.97–1.04 0.98–1.02 0.98–1.01 0.99–2.52 1.14–9.26
0.03 0.15
