Japanese Diabetic Patients Research Articles

Normal Response of Active GLP-1 Level like Substances to Test Meal in Non-Obese Type 2 Diabetic Japanese Patients with Complications and Receiving Treatments

Background: Study has shown no significant differences in basal and postprandial plasma active glucagon-like peptide-1 (p-active GLP-1) levels following test meal (TM) between complication- and treatment-naive non-obese Japanese patients with type 2 diabetes (T2DM) and controls. Methods: In non-obese Japanese patients with T2DM (n=23, group 1) and healthy individuals as control (n=13, group 2), blood levels of plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR) and p-active GLP-1 like substances (p-active GLP-1-S) were measured 0, 30, and 60 min after TM (520-560 kcal. 23% fat, 60% carbohydrate and 17% protein). HbA1c levels were also measured in the groups. Patients with mean of 9.2 years disease had various complications and treatment with diet, exercise and/or oral medical drugs except incretin-related drugs for hyperglycemia. Results: There was no significant difference in mean of sex, age, or BMI between groups. Means of HbA1c and basal and postprandial PG with area under curve (AUC), and HOMA-R were significantly higher in group 1 than in group 2. Means of HOMA-β and insulinogenic index after ingestion of TM were significantly lower in group 1 than in group 2. However, there were no significant differences in means of basal and postprandial with AUC levels of s-IRI, s-CPR and p-active GLP-1-S levels between groups. Conclusion: These results indicated that a response of p-active GLP-1-S to TM in non-obese Japanese patients with T2DM associated with a long duration of disease, various complications and various treatments with except incretin-related drugs was similar to those in non-obese healthy individuals.

Efficacy and safety of metformin for treatment of type 2 diabetes in elderly Japanese patients

The maximum dosage of metformin allowed for clinical use in Japan is much less than half that in Western countries, making it difficult to apply the results of clinical trials in Western countries to Japanese patients. In particular, the efficacy and safety of metformin in elderly patients are largely unknown. Among 1508 patients who were newly prescribed metformin at our hospital from 2000-2006, patients with sufficient clinical data were retrospectively studied for the safety (n=1132) and efficacy (n=568) of the drug. Of 568 patients in whom the efficacy of metformin was analyzed, 180 patients (31.7%) were elderly, aged 65 years or over. Metformin was effective for the treatment of type 2 diabetes in Japanese patients, with significant improvement in HbA1c level at all time-points after 1 month, with the largest decrease by approximately 0.9% in patients treated with 750 mg/day and approximately 0.7% in those treated with 500 mg/day, at 4 months. Metformin improved glycemic control in elderly patients as well as non-elderly patients. The efficacy was independent of age, sex, degree of obesity and concomitant use of other drugs. No significant difference was observed in elevated lactic acid levels between elderly and non-elderly patients. No case of lactic acidosis was observed. These results suggest that the efficacy of metformin in Japanese elderly patients with type 2 diabetes is not different from that in non-elderly patients, and that its safety might be linked to specific and well-documented contraindications rather than age itself.

Differences in the humoral autoreactivity to zinc transporter 8 between childhood- and adult-onset type 1 diabetes in Japanese patients

The aim of this study was to evaluate the humoral autoreactivity to zinc transporter 8 (ZnT8) depending on the clinical phenotype of type 1 diabetes (T1D). ZnT8 autoantibodies (ZnT8A) were determined by radioimmunoassay using carboxy-terminal ZnT8 constructs in 57 childhood-onset, 97 adult-onset, and 85 fulminant T1D. The ZnT8A frequency was higher in childhood-onset patients and decreased with increasing age of onset from 70% to 24% (P(trend)<0.005). None of the patients with fulminant T1D was positive for ZnT8A. There were at least two distinct ZnT8A epitope patterns associated with the aa325-restriction, childhood-onset patients have aa325-nonrestricted response more frequently compared to the adult-onset group (P<0.05). The level of ZnT8A was inversely associated with the copy number of HLA-DR4 allele (P<0.05). These results suggest differences in the humoral autoreactivity to ZnT8 depending on the clinical phenotype, which should provide strategy for autoantibody measurement in subjects to allow early diagnosis of autoimmune T1D.

The Basis of Platelets

Platelet activation subsequent to the adhesion of platelets to the vascular wall results in the release of mediators that promote platelet aggregation, which plays a pivotal role in the development of the polyvascular atherosclerotic disease that can be referred to by the acronym 'ATIS' (AtheroThrombosIS). The currently available antiplatelet drugs used to prevent vascular events in patients with cardiovascular disease, including peripheral arterial disease (PAD), include aspirin and thienopyridines such as clopidogrel. These drugs decrease platelet aggregability, each of them by inhibiting a different pathway of platelet activation and recruitment. Aspirin acts by inhibiting thromboxane A2 (TXA2) formation through the inhibition (acetylation) of cyclo-oxygenase. On the other hand, thienopyridines suppress the platelet aggregation adenosine diphosphate (ADP) pathway by inhibiting the platelet P2Y12 subtype of the ADP receptor. The results of the large ATT (Antithrombotic Trialists' Collaboration) meta-analysis of published clinical studies on aspirin, reported in 2002, confirmed the previous meta-analysis and major trials that treatment with aspirin (mixed with other antiplatelet agents in these large meta-analyses) can prevent vascular events in high-risk patients with cardiovascular disease. However, it must be stressed that specifically in PAD patients no significant effect of aspirin was demonstrated in a more recent meta-analysis. This was also the case for primary and secondary prevention in diabetic patients. In keeping with these observations, neither a five-year follow-up study of Japanese diabetic patients in the JPAD (Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes) study, a seven-year follow-up study of UK diabetic patients with PAD in the POPADAD (Prevention of Progression of Arterial Disease and Diabetes) study, nor a very recent Scottish study in the same population of diabetics with PAD revealed a significant beneficial effect for aspirin in preventing ischaemic events. This failure may be a consequence of more rapid recovery of platelet aggregability following each dose of aspirin in these PAD or diabetic populations, with the accelerated platelet turnover resulting in a condition of aspirin resistance. Results of the large scale CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) trial that evaluated clopidogrel in patients with cerebral infarction, myocardial infarction or PAD have found clopidogrel to be significantly more effective than aspirin in preventing ischaemic events in patients with PAD. Furthermore, a subgroup analysis of the study has confirmed the efficacy of clopidogrel in diabetic patients with PAD, showing a significant reduction of events in clopidogrel-treated, compared with aspirin-treated, diabetic patients. These results are also likely to be attributable to the greater frequency of aspirin resistance in aspirin-treated patients in these populations (diabetics and/or PAD). Platelets, through activation and aggregation, have an important role in ATIS. However, although antiplatelet therapy with low-dose aspirin has been reported to prevent vascular events in high-risk patients with cardiovascular disease, recent studies in patients with PAD or diabetes mellitus have failed to support the efficacy of aspirin in preventing vascular events in these patient populations. In contrast, clopidogrel appears to be a useful antiplatelet agent in the prevention of vascular events in patients with PAD or diabetes.

Surrogate index for insulin sensitivity composed of factors not using glucose and insulin in Japanese patients with diabetes.

The aim of the present study is to propose a novel index of insulin sensitivity instead of homeostasis model assessment of insulin resistance (HOMA-IR), which has a fundamental limitation of validity when applied to subjects with lower insulin secretions or high fasting plasma glucose (FPG) levels. A total of 25 apparently healthy subjects and 24 patients with type 2 diabetes participated in the study. We assessed relationships of glucose infusion rate (GIR), obtained by using the euglycemic hyperinsulinemic glucose clamp technique, with other measurements of metabolic and anthropometric parameters. In multiple regression analysis, a model including log-transformed (log) triglyceride/log high-density lipoprotein cholesterol and waist circumference as predictive variables showed the strongest contribution rate to explain GIR as an outcome variable (R (2) = 0.710). The validity of estimated GIR (EGIR) calculated from the regression equation composed of these factors was further tested in another group of patients including type 1, type 2 and pancreatic diabetes in whom HOMA-IR could not be used as a result of either high FPG or low fasting insulin level, or both. Even in those patients, EGIR showed a good positive relationship with measured GIR (r = 0.681, P < 0.0001). The proposed index without HOMA-IR can adequately show insulin sensitivity in Japanese diabetic patients, even in cases with the limitation of HOMA-IR application. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00076.x, 2010).

P2-8 Clinical utility of nerve conduction studies of the foot for the early detection of subclinical polyneuropathy in Japanese diabetic patients

P2-8 Clinical utility of nerve conduction studies of the foot for the early detection of subclinical polyneuropathy in Japanese diabetic patients

Effects of renal dysfunction on cardiovascular events in diabetic patients with hypertension: Challenge-DM Study subgroup analysis

This study investigated the relation between renal dysfunction and cardiovascular events in patients from the Challenge-DM Study (a large-scale investigation of Japanese diabetic patients with hypertension on candesartan therapy). The subjects were 4706 patients in whom renal function could be assessed at the time of registration among 16860 patients analyzed in the Challenge-DM Study. The definition of renal dysfunction (low GFR) was an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) calculated by the formula for Japanese. The low GFR group was older, and had a high proportion of females and a high prevalence of cerebrovascular or cardiovascular disease (CVD) compared to the normal GFR group (eGFR ≥ 60 ml/min/1.73 m(2)). Univariate Cox regression analysis of cardiovascular events showed a significant increase in the incidence of primary events and total events in the low GFR group. Among patients <65 years old, the same results were obtained, but no differences were found between the low GFR and normal GFR groups aged over 65 years. Multivariate Cox regression analysis was done with patient characteristics at registration and the presence/absence of achieving the target blood pressure and HbA(1c) before the event as explanatory variables. As a result, low GFR was not the main cause of cardiovascular events, but it had a significant influence on primary events and total events among patients <65 years old. Low GFR may be an independent risk factor for cerebrovascular and CVD among young and middle-aged Japanese diabetic patients with hypertension on candesartan therapy.

Efficacy and adverse effects of low-dose nateglinide in early type 2 diabetes: comparison with acarbose in a crossover study

Recent studies have suggested that treatment of type 2 diabetes soon after diagnosis of diabetes correlates with a long-term reduction in the risk of macroangiopathy. An open-label prospective crossover trial was performed to compare the efficacy and adverse effects of low-dose nateglinide with those of acarbose. The subjects were 23 early type 2 Japanese diabetic patients who were oral hypoglycemic agent naive and whose HbA1C levels were 6.0–6.9%. Twelve patients received 90 mg/day of nateglinide and 11 patients received 150 mg/day of acarbose. After 12 weeks of either therapy, the drugs were switched and treatment was continued for another 12 weeks. Each patient was requested to complete a questionnaire on complications after the completion of each treatment. HbA1C decreased from a mean baseline of 6.7 ± 0.2 to 6.4 ± 0.3% with nateglinide and to 6.5 ± 0.3% with acarbose. Decreases of HbA1C in nateglinide were larger than those in acarbose, albeit statistically insignificant (p = 0.073). Symptoms related to hypoglycemia were scarcely observed with either treatment. Abdominal fullness/borborygmi were frequently reported by patients on acarbose but were absent or mild in those on nateglinide. After the completion of the study, most patients favored nateglinide over acarbose. Our results suggest that the effects of low-dose nateglinide on postprandial hyperglycemia of early type 2 diabetes are equivalent to those of acarbose, with the added advantage of minimal side effects.

Elevated serum levels of interleukin-18 in patients with overt diabetic nephropathy: effects of miglitol

Interleukin-18 (IL-18), a pro-inflammatory cytokine, is a predictor of cardiovascular and renal disease in diabetic patients. Postprandial hyperglycemia is one of the important factors contributing to an increase in the circulating pro-inflammatory cytokine levels. This study investigated the effect of miglitol, an α-glucosidase inhibitor, on postprandial hyperglycemia and IL-18 levels in diabetic patients with nephropathy. Fifteen Japanese diabetic patients with persistent proteinuria and preserved renal function were recruited. The patients received 50 mg miglitol thrice daily after the baseline examinations and were followed up for 12 weeks. A meal tolerance test was performed on eight patients at baseline and week 12. The fasting miglitol concentration was measured in seven patients just before the meal tolerance test. There were no changes in the body weight, blood pressure, liver and renal function, and proteinuria from baseline to week 12. However, the levels of glycated hemoglobin and interleukin 18 significantly decreased from baseline to week 12. During the meal tolerance test, plasma glucose was significantly decreased 60 min after treatment with miglitol, whereas the serum concentration of insulin was not changed. Fasting and postprandial levels of IL-18 were significantly decreased from baseline to week 12. Serum miglitol concentrations showed a significantly negative correlation with eGFR (r = -0.82, p = 0.02). However, the serum miglitol concentrations did not changed during the course of this study. Miglitol improved postprandial hyperglycemia and reduced serum IL-18 levels in patients with stage 3 diabetic nephropathy. Miglitol may therefore prevent atherosclerotic diseases and diabetic micro-vascular complications through decreasing glucose swings and/or the circulating IL-18 level.

Validity of haemoglobin A1c and glycoalbumin for an appropriate evaluation of glycaemic control in Japanese diabetic patients with chronic renal failure.

Sir, Although the validity of glycoalbumin (GA) instead of haemoglobin A1c (HbA1c) measurement in patients on haemodialysis (HD) has recently been discussed by some investigators [1,2], an appropriate indicator for glycaemic control in patients with pre-dialysis chronic renal failure (CRF) has only rarely been reported [1]. The application of erythropoietin (EPO) for the treatment of renal anaemia increases the proportion of young erythrocytes over old erythrocytes in peripheral blood [3], and HD procedure per se causes the mechanical destruction of red blood cells (RBC). These conditions may reduce the half-life of HbA1c. On the other hand, GA is affected by an accelerated turnover of albumin in the case of nephrotic syndrome frequently observed in pre-dialysis patients due to a massive loss of protein into the urine [2]. The aim of the present study is to evaluate the validity of both indicators in Japanese patients with diabetes separately according to their CRF stage, either undergoing HD or not and either being treated with EPO or not.

Seasonal fluctuations of glycated hemoglobin levels in Japanese diabetic patients

Aims We examined whether glycated hemoglobin (HbA 1C) levels of Japanese diabetic patients showed seasonal fluctuations. Methods Subjects included 2511 diabetic patients who regularly visited a single diabetic outpatient clinic for 10 years. A total of 253,477 HbA 1C measurements, as well as sex, age, BMI, type of diabetes, and mode of therapy were extracted from a hospital-based database. For the cross-sectional and longitudinal analyses, average monthly HbA 1C values of subjects and amplitudes of seasonal fluctuations were calculated. For the time-series analysis, seasonal adjustment factors of each subject were classified as complete, incomplete, or no fluctuation. Results Subjects showed a clear seasonal fluctuation of HbA 1C levels, with highest levels in March (7.69%) and lowest levels in August (7.46%; p < 0.001). The amplitudes of the seasonal fluctuations were associated with the mean HbA 1C levels. The time-series analysis showed that 78.3% of patients had complete or incomplete seasonal fluctuations. HbA 1C levels were highest in winter–spring and lowest in summer–autumn in most patients; however, some patients showed a reverse pattern. Conclusions Seasonal fluctuations of HbA 1C levels were recognized in most of the Japanese diabetic patients. Physiological or metabolic factors related to temperature may be the main cause of seasonal fluctuations in HbA 1C levels.

Influence of BMI, Age and Duration of Diabetes Mellitus on Glycaemic Control with Twice-Daily Injections of Biphasic Insulin Aspart 30 versus Multiple Daily Injections of Insulin Aspart (JDDM 18)

Good glycaemic control in patients with diabetes mellitus often requires insulin supplementation therapy. Recent developments of analogue insulin and premixed formulations have increased the therapeutic options for patients who need such therapy. This study aimed to retrospectively clarify appropriate treatment regimens according to age, body mass index (BMI) and duration of diabetes in Japanese patients with type 2 diabetes previously entered in an open-label, randomized trial that compared convenience-oriented biphasic insulin aspart 30 versus multiple injections of insulin aspart with or without NPH insulin. Japanese insulin-naïve patients were randomized to receive either biphasic insulin aspart 30 twice daily or insulin aspart three times daily with or without multiple injections of NPH insulin for a treatment period lasting 6 months. Reduction of glycosylated haemoglobin (HbA(1c)) at the end of 6 months was not different in the two treatment groups irrespective of BMI, age and duration of diabetes. However, the achievement rate of HbA(1c) <7.0% was significantly higher in patients with a BMI <25 kg/m2 in the multiple-injection group and tended to be higher in patients with a diabetes duration <10 years in the twice-daily injection group. Twice-daily injections of biphasic insulin aspart 30 may be more suitable for obese patients whereas multiple injections of insulin aspart with or without NPH insulin may be preferable for those with a longer duration of diabetes.

Phenotypical variety of insulin resistance in a family with a novel mutation of the insulin receptor gene

A novel mutation of insulin receptor gene (INSR gene) was identified in a three generation family with phenotypical variety. Proband was a 12-year-old Japanese girl with type A insulin resistance. She showed diabetes mellitus with severe acanthosis nigricans and hyperinsulinemia without obesity. Using direct sequencing, a heterozygous nonsense mutation causing premature termination at amino acid 331 in the alpha subunit of INSR gene (R331X) was identified. Her father, 40 years old, was not obese but showed impaired glucose tolerance. Her paternal grandmother, 66 years old, has been suffered from diabetes mellitus for 15 years. Interestingly, they had the same mutation. One case of leprechaunism bearing homozygous mutation at codon 331 was identified. These findings led to the hypothesis that R331X may contribute to the variation of DM in the general population in Japan. An extensive search was done in 272 participants in a group medical examination that included 92 healthy cases of normoglycemia and 180 cases already diagnosed type 2 DM or detected hyperglycemia. The search, however, failed to detect any R331X mutation in this local population. In addition, the proband showed low level C-peptide/insulin molar ratio, indicating that this ratio is considered to be a useful index for identifying patients with genetic insulin resistance. In conclusion, a nonsense mutation causing premature termination after amino acid 331 in the alpha subunit of the insulin receptor was identified in Japanese diabetes patients. Further investigations are called for to address the molecular mechanism.

Comparative Study of Low-dose Pioglitazone or Metformin Treatment in Japanese Diabetic Patients with Metabolic Syndrome

The aim of this study was to determine whether a relatively low dose of pioglitazone or metformin was effective in diabetic patients with metabolic syndrome. Fifty diabetic patients with metabolic syndrome were randomly assigned to a low-dose pioglitazone (15 mg/day) treatment group or a low-dose metformin (500 mg/day) treatment group. Drugs were administered for 12 weeks. Systolic and diastolic blood pressure, heart rate, body mass index, triglyceride (TG), HDL and LDL-cholesterol, fasting plasma glucose (FPG), fasting plasma insulin (IRI), postprandial glucose, and HOMA-IR in the 75gOGTT, HbA1c, high-sensitivity CRP (hs-CRP) determined by cervical artery echography, and pulse wave velocity (PWV) were measured before/after 12-week drug administration. Significant decreases in HbA1c and HOMA-IR were noted in the pioglitazone group, along with significant decreases in TG, AST, ALT, blood pressure, hs-CRP and PWV. Significant decreases in HbA1c, HOMA-IR, BMI and waist circumference were noted in the metformin group. The pioglitazone group significantly improved the values for ALT, systolic blood pressure, hs-CRP and PWV compared to the metformin group. However, the metformin group demonstrated significant improvement in BMI compared with the pioglitazone group. Using a low dose regimen, pioglitazone significantly improved blood pressure and hepatic function and may be more effective than metformin to reduce risk factors in Japanese diabetic patients with metabolic syndrome at preventing atherosclerosis.

Characteristics of sleep-disordered breathing in Japanese patients with type 2 diabetes mellitus

Sleep-disordered breathing (SDB), especially sleep apnea-hypopnea syndrome, is often observed in patients with type 2 diabetes mellitus; but there are only a few studies on SDB in Japanese diabetic subjects. We investigated the prevalence of SDB in diabetic patients; associations between severity of sleep apnea (SA) and clinical factors, visceral fat, and adiponectin; and associations between type of SA and clinical factors. In the present study, 40 Japanese diabetic patients underwent overnight cardiorespiratory monitoring, and night and morning measurements of serum adiponectin concentrations. Sleep apnea was detected in Japanese diabetic patients at a high prevalence (77.5%). The following variables were associated with SDB: age, body mass index, estimated visceral fat area, and nocturnal reduction in serum adiponectin concentrations. The prevalence of central sleep apnea (CSA, ≥5/h) was 32.3% among diabetic SDB patients. Diabetic SDB patients with CSA had higher hemoglobin, increased intima-media thickness, and higher plasma brain natriuretic peptide levels than those without CSA (<5/h). In conclusion, our study demonstrated a high prevalence of SDB in Japanese diabetic patients, which correlated with visceral fat area and adiponectin. A high frequency of CSA was noted in diabetic SDB patients, together with high hemoglobin, high brain natriuretic peptide, and increased intima-media thickness. The present results of prevalence of SDB may be relevant to the higher incidence of cardiovascular disease in diabetic patients, which need to be clarified in future studies.

Safety and benefits of a tablet combining losartan and hydrochlorothiazide in Japanese diabetic patients with hypertension

This study was conducted to determine the effects of a tablet combining losartan/hydrochlorothiazide (L/HCTZ) in comparison with losartan alone in Japanese diabetic patients with hypertension. Thirty consecutive Japanese diabetic patients with hypertension were randomly assigned to group A, receiving losartan alone for the first 3 months, then L/HCTZ for the next 3 months, or group B, receiving L/HCTZ for the first 3 months, then losartan alone for the next 3 months. Clinical and biological parameters were obtained before, and 3 and 6 months after the start of this study. The decreases in systolic and diastolic blood pressure (BP) during treatment with L/HCTZ were significantly greater than in treatment with losartan alone. Both treatments significantly and similarly decreased urinary albumin excretion, the cardio-ankle vascular index (CAVI) and augmentation index (AI). There was no significant difference in metabolic change during both the mono- and combination pharmacotherapies. The tablet combining L/HCTZ significantly reduced systolic and diastolic BP compared with the losartan monotherapy, and offered benefits similar to losartan monotherapy for albuminuria, arterial stiffness assessed by the CAVI and AI, and metabolic effects. Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic patients with hypertension.

Higher Levels of Urinary Albumin Excretion Within the Normal Range Predict Faster Decline in Glomerular Filtration Rate in Diabetic Patients

OBJECTIVETo assess the relationship between albuminuria, including elevation within the normal range, and decline in glomerular filtration rate (GFR) in diabetic patients.RESEARCH DESIGN AND METHODSA total of 5,449 Japanese diabetic patients were categorized according to sex and urinary albumin-to-creatinine ratio (ACR; <5, 5–9, 10–29, 30–99, 100–299, 300–999, 1,000–2,999, and ≥3,000 mg/g) and followed for at least 5 years. The rate of change in estimated GFR (eGFR) adjusted for age and baseline eGFR was compared among ACR categories.RESULTSA higher baseline ACR predicted a faster decline in eGFR for both sexes. Even within the normal range (<30 mg/g), ACR ≥10 mg/g in women and ≥5 mg/g in men was associated with a significantly greater rate of decline in eGFR relative to subjects with ACR <5 mg/g.CONCLUSIONSElevated ACR, even within the normal range, is associated with a faster decline in eGFR in diabetic patients.

Waist Circumference as a Cardiovascular and Metabolic Risk in Japanese Patients With Type 2 Diabetes

Excess waist circumference (WC) is a frequently used indicator of abdominal obesity and/or cardiovascular disease (CVD) risk. Nonetheless, search of the literature revealed no prospective studies on the association between WC and CVD events in diabetic patients. In this study, the clinical significance and implications of WC as a cardiovascular and metabolic risk indicator was prospectively investigated in Japanese patients with type 2 diabetes. For this purpose, baseline data on WC, hypertension, and dyslipidemia were collected and subsequent CVD (coronary heart disease and stroke) events during the following 8 years were studied in 1,424 Japanese type 2 diabetic patients, and the cross-sectional/longitudinal associations between WC and CVD risk factors/events were analyzed. Mean WC levels were significantly increased according to the number of coexisting risk factors. However, no significant difference in mean WC between subgroups with and without CVD events was noted, and excess WC alone was not predictive of subsequent CVD events either in male or female subjects even after adjustment for age, smoking, hypertension, and dyslipidemia. In female patients, excess WC (> or =80 cm) was predictive of CVD events only with the coexistence of hypertension. In Japanese diabetic patients, excess WC alone, although a good marker for clustering of CVD risk factors, did not raise the risk of CVD events unless accompanied by hypertension in female patients. Further investigations are necessary before WC as a risk factor can be utilized in clinical settings for the management of diabetes in this population.

Influence of Statins on Glucose Tolerance in Patients with Type 2 Diabetes Mellitus: Subanalysis of the Collaborative Study on Hypercholesterolemia Drug Intervention and their Benefits for Atherosclerosis Prevention (CHIBA Study)

the atorvastatin group (p=0.026), whereas no significant difference was observed in the pitavastatin group (Table 1). In the atorvastatin group, but not in pitavastatin group, the HbA1c level also tended to increase (p=0.098). Since glycoalbumin is known to reflect glycemic control over a shorter period of time than HbA1c, only glycoalbumin might have detected a slight glycemic change during a treatment period of 12 weeks in this relatively small study. There were no significant changes in fasting plasma glucose, insulin or the homeostasis model assessment ratio, but all of these values tended to decrease in the pitavastatin group. To date, adverse effects of atorvastatin on glucose tolerance have not been clearly demonstrated in clinical studies carried out in Western countries; however, several reports have suggested the deterioration of glycemic control with atorvastatin use for 3 to 4 months in Japanese diabetic patients as referred to by Yamakawa et al.. Recently, a PROVE-IT substudy has shown that high-dose atorvastatin treatment is associated with worse glycemic control. An in vitro study demonstrated that atorvastatin near the physiological concentrations suppressed glucose transporter GLUT4 expression in 3T3-L1 adipose cells. Since it has been suggested that the insulin-secreting capacity of pancreatic β-cells is lower in Japanese than Caucasians, even a slight negative influence on insulin sensitivity in the peripheral tissue may affect glycemic control in Japanese patients. Previous reports, together with our findings suggest that atorvastatin, but not pitavastatin, affects glycemic control in some Japanese diabetic patients. Larger clinical trials are required to draw a conclusion. In the previous issue of J Atheroslcer Thromb, Yamakawa et al. showed a significant increase in glycohemoglobin A1c (HbA1c) level in diabetic patients treated with atorvastatin, but not in patients given pitavastatin or pravastatin. Although the finding is intriguing, their study could not exclude bias because it was retrospective and recruited subjects only at a single hospital. Here we report the results of glycemic control subanalysis in a multicenter prospective comparative study of pitavastatin and atorvastatin (CHIBA study). In the original study, 204 Japanese patients with hypercholesterolemia recruited at 39 medical facilities were randomized to receive either 2 mg pitavastatin or 10 mg atorvastatin daily for 12 weeks, and the percent change from baseline in lipid parameters after 12 weeks of treatment was evaluated . Among 99 patients with type 2 diabetes included in the study, 45 patients (23 on pitavastatin and 22 on atorvastatin) at 16 centers were subjected to the evaluation of parameters related to glucose tolerance. Serum lipid levels at the baseline were similar between groups. No changes were made in types or doses of medications used to treat diabetes or hypertension, or in lifestyle guidance throughout the study period. After 12 weeks of statin treatment, serum glycoalbumin had significantly increased by 0.67±1.31% compared to the baseline in

Transient Anti-GAD Antibody Positivity and Acute Pancreatitis with Pancreas Tail Swelling in a Patient with Susceptible Haplotype for Type 1 Diabetes Mellitus

A 57-year-old man was admitted to our hospital complaining of poor appetite. He had been diagnosed with diabetes mellitus and was anti-GAD antibody (GAD-Ab) negative 1 year previously, at the age of 56 years old. Abdominal CT revealed pancreas tail swelling; elastase-I level was elevated and he was diagnosed with pancreatitis. The level of GAD-Ab was increased and HLA haplotype was DRB1*0901-DQB1*0303, which is seen frequently in type 1 diabetic Japanese patients. However, his endogenous insulin secretion ability was not deteriorated. After elastase-I level and pancreas swelling improved, GAD-Ab returned to a normal range. One year after the onset of pancreas swelling, he was still not in an insulin-dependent state. In this case, transient GAD-Ab positivity with susceptible haplotype for type 1 diabetes mellitus might have been induced by a GAD antigen discharged from the destroyed islet due to pancreatitis.