Japanese Diabetic Patients Research Articles

Identifying Risk Factors for Clinically Significant Diabetic Macula Edema in Patients with Type 2 Diabetes Mellitus

It is known that clinic blood pressure (BP), gender, cigarette smoking, dyslipidemia, anemia and thiazolidenediones (TZD) treatment are predictors for clinically significant diabetic macula edema (CSDME). We examined a most risky factor for CSDME in Japanese patients with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) confirmed using optical coherence tomography by multiple regression analysis (MRA). As the risk factors, wakening-up BP was added to such factors. Seven diabetic Japanese patients with CSDME (group 1) and 124 subjects without CSDME (group 2) assonated with DR using optical coherence tomography were studied. The durations of T2DM in groups 1 and 2 were 15±10 years and 20±15 years, respectively. There was no statistically difference in means of gender, duration, age, body mass index (BMI), HbA1c, TC, LDL and TC/HDL, serum creatinine, urinary albumin excretion rate, and clinic BP between two groups. Morning systolic home BP (MSHBP), cigarette smoking and foveal thickness were significantly (p<0.001) higher in group 1 than group 2, whereas visual acuity was significantly (p<0.00?) lower in group 1 than in group 2. The patients in both groups had received various kinds of drugs for hyperglycemia, hypertension and others. There were no significant differences in the variables in both groups. MRA revealed that MSHBP, cigarette smoking and pioglitazone as TZD treatment were significantly positive predictors for CSDME, while BMI had a significantly negative predictor. Other variables were not significantly correlated to CSDME. The review summarizes a multiple regression analysis revealed that MSHBP makes an addition to predictive factors for CSDME among risk factors reported previously in patient with T2DM.

Seasonal fluctuations of glycated hemoglobin levels in Japanese diabetic patients: effect of diet and physical activity

Aims We examined whether diet and/or physical activity contribute to seasonal variation of hemaglobin A1c (HbA1c) in Japanese diabetic patients.

Leisure-time physical activity is a significant predictor of stroke and total mortality in Japanese patients with type 2 diabetes: analysis from the Japan Diabetes Complications Study (JDCS)

Our aim was to clarify the association between leisure-time physical activity (LTPA) and cardiovascular events and total mortality in a nationwide cohort of Japanese diabetic patients. Eligible patients (1,702) with type 2 diabetes (mean age, 58.5 years; 47% women) from 59 institutes were followed for a median of 8.05 years. A comprehensive lifestyle survey including LTPA and occupation was performed using standardised questionnaires. Outcome was occurrence of coronary heart disease (CHD), stroke and total mortality. The adjusted HR and 95% CI were calculated by Cox regression analysis. A significant reduction in HR in patients in the top (≥ 15.4 metabolic equivalents [MET] h/week) vs the bottom tertile (≤ 3.7 MET h/week) of LTPA, adjusted by age, sex and diabetes duration, was observed in stroke (HR 0.55, 95% CI 0.32, 0.94) and total mortality (HR 0.49, 95% CI 0.26, 0.91) but not in CHD (HR 0.77, 95% CI 0.48, 1.25). The HR for stroke became borderline significant or nonsignificant after adjustment for lifestyle or clinical variables including diet or serum lipids. The significantly reduced total mortality by LTPA was independent of these variables and seemed not to be, at least mainly, attributed to reduced cardiovascular disease. In Japanese persons with type 2 diabetes, LTPA of 15.4 MET h/week or more was associated with a significantly lower risk of stroke partly through ameliorating combinations of cardiovascular risk factors. It was also associated with significantly reduced total mortality but independently of cardiovascular risk factors or events. These findings, implying differences from Western diabetic populations, should be considered in the clinical management of East Asians with diabetes.

Effect of Low-Dose Aspirin on Primary Prevention of Cardiovascular Events in Japanese Diabetic Patients at High Risk

Benefit of low-dose aspirin for primary prevention of cardiovascular events in diabetes remains controversial. The American Diabetes Association (ADA), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend aspirin for high-risk diabetic patients: older patients with additional cardiovascular risk factors. We evaluated aspirin's benefit in Japanese diabetic patients stratified by cardiovascular risk. In the JPAD trial, we enrolled 2,539 Japanese patients with type 2 diabetes and no history of cardiovascular disease. We randomly assigned them to aspirin (81-100 mg daily) or no aspirin groups. The median follow-up period was 4.4 years. We stratified the patients into high-risk or low-risk groups, according to the US recommendation: age (older; younger) and coexisting cardiovascular risk factors. The risk factors included smoking, hypertension, dyslipidemia, family history of coronary artery disease, and proteinuria. Most of the patients were classified into the high-risk group, consisting of older patients with risk factors (n=1,804). The incidence of cardiovascular events was higher in this group, but aspirin did not reduce cardiovascular events (hazard ratio [HR], 0.83; 95% confidence interval [CI]: 0.58-1.17). In the low-risk group, consisting of older patients without risk factors and younger patients (n=728), aspirin did not reduce cardiovascular events (HR, 0.55; 95% CI: 0.23-1.21). These results were unchanged after adjusting for potential confounding factors. Low-dose aspirin is not beneficial in Japanese diabetic patients at high risk.

4．ADL低下のリスクと対応策

The purpose of the present investigation was to explore the process towards functional disability and predicting factors in Japanese diabetic elderly. We recruited 317 older patients aged 65 or over among participants in the large-scale prospective study of the Japanese Elderly Diabetes Intervention Trial (J-EDIT). We analyzed the changes of daily life function prospectively for 6 years. Information about diabetes, blood examinations and complications was obtained, and basic activity of daily living (ADL) and instrumental ADL (IADL) were assessed by total Barthel index score and the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG index), respectively. During 6 years of follow-up, 13.6% of subjects had developed a new ADL disability (bADL) and 38.3% had developed a new functional impairment assessed by TMIG index. In the 65-74 years age group, basic ADL decreased only in males, while females became functionally impaired. In 75-84 years age group, basic and IADL decreased in both men and women. Older age and metabolic syndrome negatively affected ADL, while baseline IADL impairment, cognitive dysfunction, physical inactivity, and insulin therapy were significant predictors of a future decline in the IADL. This study identified the disability process and prognostic factors, including the future decline of basic ADL and IADL in diabetic elderly patients. There are modifiable factors for ADL impairment, comprehensive treatment and care are required to keep Japanese diabetic elderly patients healthy in daily life functioning.

Obstructive sleep apnea syndrome causes a pseudo-Cushing’s state in Japanese obese patients with type 2 diabetes mellitus

Activation of the hypothalamic-pituitary-adrenal axis has been reported in some patients with the obstructive sleep apnea syndrome (OSAS). In current study, we investigated whether OSAS affect the screening test for subclinical Cushing's disease using 0.5 mg overnight dexamethasone suppression test (DST) in Japanese obese diabetic patients with OSAS. Among Japanese obese patients with type 2 diabetes mellitus who had been hospitalized in our department, we selected 20 patients with moderate to severe untreated OSAS (apnea-hypoxia index, AHI, of ≥15 events/hour). All patients underwent 0.5 mg DST. The same test was repeated in patients with positive response of it within a few days after continuous positive airway pressure (CPAP) therapy. We found that five patients showed positive response of DST (25%). Three of these patients continued to use CPAP, and they showed normal response of DST after CPAP therapy. Serum cortisol after 0.5 mg DST measured before CPAP therapy correlated significantly with fasting serum cortisol level (r=0.764, p<0.0001), but not with various clinical parameters, including AHI (p=0.784), body mass index (p=0.984), waist circumference (p=0.957), HbA1c (p=0.261), fasting plasma glucose (p=0.420) and HOMA-IR (p=0.500). Our study show that OSAS causes a pseudo-Cushing's syndrome in obese patients with type 2 diabetes mellitus, which phenomena can be reversed by CPAP therapy.

Improved Lipid Profiles are Associated with Reduced Incidence of Coronary Vascular Events in Asymptomatic Patients with Type 2 Diabetes and Impaired Myocardial Perfusion

Individuals with type 2 diabetes are at high risk for cardiovascular events; however, a modality that could reduce risk has not been fully evaluated. We examined the annual incidence rate of cardiovascular events in asymptomatic Japanese diabetic patients who underwent gated myocardial perfusion single-photon computed tomography (SPECT). Asymptomatic patients (n= 485) aged ≥50 years and with either a maximal carotid artery intima-media thickness of ≥1.1 mm, or urinary albumin ≥30 mg/g creatinine, or at least two of abdominal obesity, low HDL cholesterol, high triglyceride levels and hypertension were evaluated at 50 institutions using gated SPECT with the stress-rest protocol and were followed up for three years. In the patients with summed stress scores (SSS) of ≥9, the initial high cardiovascular incidence rate in the first year declined significantly (p<0.001) from 21% to 2% during the second and third year. The incident rate was consistent among diabetics with low SSS during follow-up. Baseline LDL and non-HDL cholesterol levels significantly reduced (123±6.4 to 99±6.1 mg/dL; p<0.05) during the first year in diabetic patients with high SSS, but did not significantly change in diabetic patients with low (<9) SSS. The immediate improvement of lipid levels within one year correlated with the significant reduction in CVD events arising in diabetic patients with moderate or severe myocardial ischemia. Thus, rapidly lowering hyperlipidemia is very effective for patients with type 2 diabetes at high risk for cardiac events.

持続血糖測定（CGM）でみた日本人糖尿病透析患者の血糖動態

持続血糖測定（CGM）でみた日本人糖尿病透析患者の血糖動態

Japanese diabetic patients with Werner syndrome exhibit high incidence of cancer

To the Editor Diabetes is associated with the occurrence and progression of malignant tumors [1, 2]. Werner syndrome (WS), an autosomal recessive disorder classified as a progeroid syndrome, occurs because of mutation of the WRN gene encoding a RecQ-type DNA helicase. Because WS patients often have diabetes and malignant tumors, we initiated a nation-wide epidemiological survey in Japan to clarify the current relationship between the prevalence of diabetes and malignant tumors in them. We sent 6921 survey sheets to hospitals with[200 beds. This survey confirmed 336 new WS patients; detailed clinical data were obtained for 163 patients with diabetes, malignant tumors, or both [3]. These patients were categorized as diabetic (n = 102) and non-diabetic (n = 61). The correlation between diabetes and epithelial tumors (cancers) or non-epithelial tumors was examined using the chi-square test. The proportions of patients grouped according to age were 1.2, 9.8, 23.3, 62.6, and 1.8 % for patients in their 20s, 30s, 40s, 50s, and 60s, respectively. The prevalence of cancers and non-epithelial tumors was 11.7 and 19.0 %, respectively. No significant difference was observed in the morbidity rates of non-epithelial tumors in diabetic or non-diabetic patients (21.6 vs. 21.3 %, p = 0.485). However, diabetic patients showed significantly higher cancer prevalence than non-diabetic patients (16.6 vs. 4.9 %, p = 0.013). The types of malignant tumors in these patients and their prevalence rates are shown in Table 1. The prevalence of non-epithelial tumors and cancers is similar in WS patients [4]; non-epithelial tumors are seldom observed in the general population. Insulin resistance is related to the high cancer prevalence in diabetic patients [5]. Diabetes in WS patients is usually caused by high insulin resistance [6], which may contribute to cancer development. WS patients usually die in their 40s [4]. However, in our study, more than 60 % WS patients were in their 50s, which confirmed that the average life expectancy of Japanese WS patients has increased by 5–10 years. Because cancer incidence has increased with age, aging may be a risk factor for cancer development, especially in diabetic WS patients. Thus, our results demonstrate that diabetic WS patients show high cancer prevalence. It is therefore important to monitor the development of not only non-epithelial tumors but also cancers in these patients, especially when WS is complicated with diabetes. Communicated by Renato Lauro.

Risk factors for a 6‐year decline in physical disability and functional limitations among elderly people with type 2 diabetes in the Japanese elderly diabetes intervention trial

Type 2 diabetes increases the risk of disability. The purpose of this study was to clarify the explanatory factors for disability in Japanese diabetic elderly. The 6-year decline in physical disability and functional limitations was investigated among 317 elderly people with type 2 diabetes recruited in a large-scale prospective study of the Japanese Elderly Diabetes Intervention Trial. Information about diabetes, blood examinations and complications was obtained, and basic activities of daily living (ADL) and instrumental ADL (IADL) were assessed by total score of the Barthel index and the Tokyo Metropolitan Institute of Gerontology Index of Competence, respectively. After 6 years of follow up, 13.6% of patients had developed a new ADL disability and 38.3% had developed a new functional impairment. In the 65-74 years age group, basic ADL decreased only in males, whereas females became functionally impaired. In the 75-84 years age group, basic and IADL decreased in both males and females. Older age and metabolic syndrome were prognostic for impairment of basic ADL, whereas baseline IADL problems, lower cognitive function, physical inactivity and insulin therapy were significant predictors of a future decline in the IADL. This study identified several factors predicting the future decline of basic ADL and IADL in diabetic elderly patients, and provided a conceptual framework that might help to clarify the pathways leading to disability. Because the specific causes of each functional problem are modifiable, comprehensive treatment and care are needed to allow Japanese diabetic elderly patients to have more favorable living conditions.

Long‐term multiple risk factor interventions in Japanese elderly diabetic patients: The Japanese Elderly Diabetes Intervention Trial – study design, baseline characteristics and effects of intervention

To evaluate long-term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes patients. Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years. There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P < 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non-fatal events between the two groups. Composite events were also similar in the two groups. This study showed no significant differences in fatal or non-fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients.

Non‐high‐density lipoprotein cholesterol: An important predictor of stroke and diabetes‐related mortality in Japanese elderly diabetic patients

To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients. This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥ 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry. During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non-high-density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P < 0.001) for diabetes-related death and 1.008 (1.002-1.014; P < 0.001) for total diabetes-related events. Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients.

Impact of Diabetes Among Revascularized Patients in Japan and the U.S.

OBJECTIVEApproximately 25% of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have diabetes, and the diagnosis of diabetes roughly doubles the mortality risk associated with coronary artery disease. However, the impact of diabetes may differ according to ethnicity. Our objective was to examine the impact of diabetes on long-term survival among U.S. and Japanese patients who underwent PCI or CABG.RESEARCH DESIGN AND METHODSFor the current analysis, we included 8,871 patients from a Japanese multicenter registry (Coronary Revascularization Demonstrating Outcome database in Kyoto; median follow-up 3.5 years; interquartile range [IQR] 2.6–4.3) and 7,229 patients from a U.S. multipractice registry (Texas Heart Institute Research Database; median follow-up 5.2 years; IQR 3.8–6.5).RESULTSDiabetes was more prevalent among Japanese than U.S. patients (39.2 vs. 31.0%; P < 0.001). However, after revascularization, long-term all-cause mortality was lower in diabetic Japanese patients than in diabetic U.S. patients (85.4 vs. 82.2%; log-rank test P = 0.009), whereas it was similar in nondiabetic Japanese and U.S. patients (89.1 vs. 89.5%; P = 0.50). The national difference in crude mortality was also significant among insulin-using patients with diabetes (80.8 vs. 74.9%; P = 0.023). When long-term mortality was adjusted for known predictors, U.S. location was associated with greater long-term mortality risk than Japanese location among nondiabetic patients (hazard ratio 1.58 [95% CI 1.32–1.88]; P < 0.001) and, especially, diabetic patients (1.88 [1.54–2.30]; P < 0.001).CONCLUSIONSAlthough diabetes was less prevalent in U.S. patients than in Japanese patients, U.S. patients had higher overall long-term mortality risk. This difference was more pronounced in diabetic patients.

The lack of long-range negative correlations in glucose dynamics is associated with worse glucose control in patients with diabetes mellitus

Glucose dynamics measured in ambulatory settings are fluid in nature and exhibit substantial complexity. We recently showed that a long-range negative correlation of glucose dynamics, which is considered to reflect blood glucose controllability over a substantial period, is absent in patients with diabetes mellitus. This was demonstrated using detrended fluctuation analysis (DFA), a modified random-walk analysis method for the detection of long-range correlations. In the present study, we further assessed the relationships between the established clinical indices of glycemic or insulinogenic control of hemoglobin A1c (HbA1c), glycated albumin (GA), 1,5-anhydroglucitol, and urine C-peptide immunoreactivity and the recently proposed DFA-based indices obtained from continuous glucose monitoring in 104 Japanese diabetic patients. Significant correlations between the following parameters were observed: (1) HbA1c and the long-range scaling exponent α2 (r = 0.236, P < .05), (2) GA and α2 (r = 0.254, P < .05), (3) GA and the short-range scaling exponent α1 (r = 0.233, P < .05), and (4) urine C-peptide immunoreactivity and the mean glucose fluctuations (r = −0.294, P < .01). Therefore, we concluded that increases in the long-range DFA scaling exponent, which are indicative of the lack of a long-range negative correlation in glucose dynamics, reflected abnormalities in average glycemic control as clinically determined using HbA1c and GA parameters.

Intraocular pressure in Japanese diabetic patients

BackgroundTo determine whether the intraocular pressure (IOP) in diabetic patients is significantly different from that in nondiabetic patients.MethodsThe medical records of all patients who were initially examined in the Department of Ophthalmology, Kansai Medical University, Takii Hospital were reviewed. At the initial examination, patients had a detailed interview and underwent a comprehensive ophthalmic examinations. All patients were over 20 years of age and did not have glaucoma.ResultsA total of 703 patients were evaluated. The mean (±standard error) IOP of the diabetic patients was 15.5 ± 0.2 mmHg (n = 206), and was significantly higher than the 14.0 ± 0.1 mmHg (n = 497) in the nondiabetic patients (P < 0.0001). The IOP was negatively correlated with age (r = −0.202; P = 0.024) in the diabetic patients and was weakly but significantly correlated with the glycosylated hemoglobin (HbA1c) level (r = 0.240; P = 0.015) in the group with diabetic retinopathy.ConclusionThe significantly higher IOP in diabetic patients and positive correlation of IOP with HbA1c levels in patients with diabetic retinopathy indicate that IOP in diabetic patients is higher, especially in those with poor control of diabetes.

Efficacy of sitagliptin on blood glucose fluctuation in Japanese type 2 diabetic patients with basal-supported oral therapy

We retrospectively investigated the effect of adding dipeptidyl peptidase-4 (DPP-4) inhibitor and tapering sulfonylurea on blood glucose fluctuation in Asian patients with type 2 diabetes mellitus under basal-supported oral therapy (BOT). We recruited twenty-two consecutive Japanese patients with type 2 diabetes mellitus who had blood glucose fluctuation under the combination therapy of insulin glargine and glimepiride and had sitagliptin initiated with glimepiride tapared. Their hemoglobin A1c levels and mean blood glucose profiles of seven points in self-monitoring blood glucose (SMBG) were 7.4 ± 0.6% and 8.6 ± 2.0 mmol/L, respectively. Sitagliptin was initiated with the dose of 50 mg per day and titrated up to 100 mg per day when necessary. Glimepiride was withdrawn if possible. Blood glucose fluctuation was evaluated with SMBG by calculating M-value, its range (the difference of maximum and minimum blood glucose levels), and its coefficient of variation (CV). Two months after sitagliptin add-on, M-value was decreased from 19 ± 13 to 13 ± 8 (p = 0.04). Blood glucose range and CV were also improved from 9.6 ± 2.9 mmol/L to 7.9 ± 2.6 mmol/L (p = 0.01), and from 33 ± 8% to 29 ± 8% (p < 0.01), respectively. Hemoglobin A1c levels and mean blood glucose profiles were unchanged (p = 0.93 and 0.47). In conclusion, blood glucose fluctuation was significantly improved two months after adding sitagliptin and tapering glimepiride in type 2 diabetic Japanese patients who were treated by BOT with insulin glargine and glimepiride.

Potential correlation between plasma total GIP levels and body mass index in Japanese patients with types 1 or 2 diabetes mellitus

Glucose-dependent insulinotropic polypeptide (GIP) secretion in diabetic Europeans with type 1 (T1DM) and type 2 (T2DM) following test meal (TM) has been shown to be normal. In Japanese patients with T2DM, GIP secretion was also normal. We determined whether GIP secretin is influenced by various factors. Plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR), and plasma total GIP (p-total GIP) levels were measured at 0, 30, and 60 minutes after TM (560 kcal) in patients with T1DM (n = 15, group 1) and T2DM (n = 29, group 2) treated with various medications. HbA1c was also measured. At baseline, means of age, BMI, HbA1c, PG, s-CPR, SUIT (secretory unit in transplantation) and p-total GIP were significantly lower in group 1 than in group 2. Each mean of postprandial p-total GIP levels after TM in all patients was more dramatically increased than other factors. The area under the curve (AUC) of p-total GIP levels in early-phase (0 to 30 min) was significantly positively correlated with BMI in group 2 but not in group 1, and not with other factors. These results indicate that the GIP secretion after TM in diabetic Japanese patients was dramatically increased, and the AUC of GIP secretion in early-phase was positively correlated with BMI in non-obese and obese patients with T2DM, but not with T1DM. The increase was not influenced by gender, age, glycemic control, duration of disease, micro- or macro-vascular disturbances, or oral drugs.

Clinical significance of serum adiponectin in Japanese diabetic patients

To investigate the clinical significance of the serum adiponectin concentration in Japanese diabetic patients. We examined serum adiponectin levels in 1,541 diabetic patients from 2005 to 2009. The serum level of adiponectin was higher in patients with type 1 diabetes and in those receiving pioglitazone treatment than in other groups. Serum adiponectin was inversely correlated with body mass index, waist circumference, fasting plasma glucose, serum triglycerides, serum uric acid, fasting serum IRI, and HOMA-IR; it was positively correlated with age and HDL cholesterol. Serum adiponectin was significantly lower in diabetic male patients with metabolic syndrome than in those without it, and patients with more cardiometabolic risk factors also had lower adiponectin levels. Serum adiponectin was significantly lower in patients with microangiopathy than in those without (both male and female), and was also significantly lower in male patients with macroangiopathy than in those without it. Measurement of the serum adiponectin in diabetic patients is useful for assessing metabolic status and for evaluating the risk of arteriosclerosis, particularly in males.

日本人糖尿病患者におけるβ3アドレナリン受容体遺伝子ミスセンス変異と肥満, 高血圧, 内臓脂肪症候群との関連

日本人糖尿病患者におけるβ3アドレナリン受容体遺伝子ミスセンス変異と肥満, 高血圧, 内臓脂肪症候群との関連

Decreased active GLP-1 response following large test meal in patients with type 1 diabetes using bolus insulin analogues

Postprandial plasma immunoreactive active glucagon-like peptide-1 (p-active GLP-1) levels in type 1 diabetic patients who did not use bolus insulin responded normally following ingestion of test meal, while a small response of p-active GLP-1 levels was seen in type 2 diabetic patients. To determine whether p-active GLP-1 levels are affected by ingestion of test meal in type 1 diabetic Japanese patients who used bolus rapid-acting insulin analogues, plasma glucose (PG), serum immunoreactive insulin (s-IRI), serum immunoreactive C-peptide (s-CPR), and p-active GLP-1 levels were measured 0, 30, and 60 min after ingestion of test meal in Japanese patients without diabetic complications (n=10, group 1) and control subjects with normal glucose tolerance (n=15, group 2). HbA1c levels were also measured in these groups. The patients in group 1 were treated with multiple daily injections or CSII using injections of bolus rapid-acting insulin analogues before ingestion of test meal. There was no significant difference in mean of sex, age, or BMI between groups. Means of HbA1c, basal and postprandial PG, and postprandial s-IRI levels with integrated areas under curves (0-60 min) (AUC) in group 1 were significantly higher than those in group 2. Means of basal and postprandial s-CPR, and postprandial p-active GLP-1 levels with AUCs were significantly lower in group 1 than in group 2. These results indicated that postprandial p-active GLP-1 levels following ingestion of test meal in type 1 diabetic Japanese patients using bolus rapid-acting insulin analogues were decreased relative to those in controls.