Correlation between baseline serum 1,5-anhydroglucitol levels and 2-hour post-challenge glucose levels during oral glucose tolerance tests.

Since there is increasing evidence that postprandial hyperglycemia is a risk factor for the development of macrovascular complications, it is important to predict postprandial hyperglycemia in the early stages of glucose intolerance, and routine medical checkups provide a good opportunity to do so. The aim of this study was to evaluate the usability of 1,5-anhydroglucitol (1,5-AG) in routine medical checkups. The subjects were 77 Japanese men who participated in a routine medical checkup. First, we performed 75 g oral glucose tolerance tests (OGTTs), and examined the changes in glucose and 1,5-AG levels measured at 0, 30, 60, 90, 120, and 180 minutes (min). 1,5-AG levels did not significantly change until 90 min after the glucose load. Second, a linear regression analysis showed an inverse correlation between the 2-hour post-challenge glucose (2h-PG) and baseline 1,5-AG levels during the OGTT (P = 0.001, r(2) = 0.13), and the correlation was still significant after adjustment for age (2h-PG = 170 + 0.83 × (age in years) - 3.23 × (1,5-AG), P = 0.002, adjusted r(2) = 0.12). Finally, to investigate the test characteristics of 1,5-AG levels as a predictor of a 2h-PG level ≥200 mg/dL, we plotted a receiver operating characteristic (ROC) curve. The area under the ROC curve was 0.78, and the maximal sum of sensitivity and specificity (78% and 72%, respectively) was obtained at a 1,5-AG cutoff level of <14.2µg/mL. We conclude that 1,5-AG values may provide an ancillary predictor of 2h-PG of 75 g OGTTs in routine medical checkups.

[Need for Prescription Suggestions for Long-term Inpatients in the Psychiatric Ward].

Additional fees for ward pharmacists' services have been valued for hospitals in Japan. However, the calculation period for services provided to inpatients in the psychiatric ward is limited to 8 weeks. This study aimed to reveal the need for the services of pharmacists in the hospital ward for inpatients hospitalized for >8 weeks in the psychiatric ward. Patients who were hospitalized in the psychiatric ward from September 2016 to February 2017 were analyzed retrospectively. The pharmacists suggested prescriptions for inpatients admitted for >8 weeks, similar to those admitted for <9 weeks, and this supported pharmacotherapy without exacerbating patient outcomes. Moreover, significant decreases in benzodiazepine doses were found between the prior and post prescription suggestions of the pharmacist for inpatients >8 weeks of admission. Healthcare expenditures were also reduced. These results suggest that the prescriptions suggested by pharmacists for inpatients admitted for >8 weeks in the psychiatric ward were useful. In conclusion, our findings show that ward pharmacists' services were necessary not only for the inpatients hospitalized for <9 weeks, but also for those hospitalized for >8 weeks.

[Effect of Digital Labels on Electronic Medical Records for Reducing the Use of Benzodiazepine Receptor Agonists].

Benzodiazepine receptor agonists (BZDs) should be appropriately used owing to the associated risks of delirium and falls. Since January 2018, the liaison team pharmacist at Iizuka Hospital has been applying digital labels with recommendations for the reduction of use and changes in the medication orders and prescriptions of BZDs on electronic medical records of patients in the surgical ward. This study aimed to verify the effectiveness of reducing the use of BZDs via the implementation of digital labels. Patients in the surgical ward were retrospectively assessed for changes in medication orders and prescription ratios of BZDs before and after the implementation of digital labels. The ratio of the number of digital labels implemented to the number of confirmations of medication orders and prescriptions of BZDs was 15.0% at the start of implementation; however, the ratio gradually and significantly decreased to 3.6%. The medication order ratio of BZDs was 52.2% before the implementation of digital labels; however, this ratio decreased to 2.7% and 5.6% immediately and 4 months after the implementation of digital labels, respectively. The present study showed that medication orders for BZDs were reduced after the implementation of digital labels and that the reduction effect was maintained for a certain period of time. Thus, the liaison team pharmacist-led approach can contribute to the proper use of BZDs.

[Evaluation of Pharmacist-led Interview before Doctor Examination for Psychiatry Outpatients].

Psychiatric treatment is shifting from hospital to ambulatory care. It is important that pharmacists positively support outpatients. Pharmacist-led interviews with outpatients have been conducted in the psychiatric department of Iizuka Hospital before examination by the doctor since 2015. Few studies in this field have reported about the effect of the pharmacist-led interviews using subjective evaluation of outpatients prior to examination by doctors. The aim of this study was to reveal this effect by the evaluation of outpatients. We conducted a questionnaire survey. More than 80% of the patients responded that it was "Good" to have an interview with the pharmacist prior to examination by the doctor. Moreover, 71.7% of the patients were "Satisfied" with the pharmacist-led interview, while 81.7% of them responded to "Agree" about continuing the interview in the future. Patients who were satisfied and wished to continue the pharmacist-led interviews were more likely to report better rapport with the doctor as well, in comparison to the patients who answered negatively. Furthermore, the patients who answered "Satisfied" were significantly less likely to forget reporting to the doctor than those who answered negatively. The pharmacist-led interviews in the psychiatric department were appreciated by the patients. In conclusion, pharmacists can facilitate communication between patients and doctors through these interviews. These results indicate that the pharmacist-led interview before the doctor examination is a useful effort from the perspective of outpatients.

Effect of antihyperglycemic drug monotherapy to prevent the progression of mild hyperglycemia in early type 2 diabetic patients: the Japan Early Diabetes Intervention Study (JEDIS).

To effectively prevent the worsening of hyperglycemia in type 2 diabetes mellitus, it is of interest to see the clinical efficacy of early introduction of pharmacotherapy in addition to lifestyle intervention which is not always easy to continue throughout life. This is a randomized unblinded comparative clinical study on suppressive effects of lifestyle intervention alone and additional monotherapies for mild hyperglycemia at an early stage of treatment-naïve type 2 diabetic patients, whose fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) are less than 140 mg/dl and 7.4%, respectively. The control group (group N = arm N) received conventional lifestyle intervention assisted by routine facilities, while the pharmacological intervention group (group D composed of 4 arms) was additionally treated by monotherapy with one of four kinds of oral antihyperglycemic agents i.e., sulfonylurea (SU), α-glucosidase inhibitor, biguanide and dipeptidyl peptidase-4 inhibitor. The participants were scheduled to follow up for 3 years to maintain glycemic control below primary endpoint which was defined as the first occurrence of FPG ≥140 mg/dl and HbA1c ≥7.4% simultaneously even by increasing doses of oral drug in group D, if necessary. The outcomes of occurrences of primary endpoint were not different between group N and group D composed of 4 arms during 3 years by Kaplan-Meyer plots (p = 0.405). On the other hand, ΔFPG (Δ: incremental change from baseline) and ΔHbA1c in group D significantly decreased when compared to those of group N during 3 years (p < 0.05 and p < 0.01 respectively). Significant reductions of ΔBMI were seen similarly in both groups throughout the study (p < 0.05), but did not differ between two groups. Among these 5 arms, significant decreases of ΔHbA1c were observed in three monotherapy arms of group D compared to arm N for 3 years (p < 0.05 or p < 0.01), except for arm SU in which ΔBMI and ΔHbA1c tended to increase at the latter half of the study. The final achievement rates of target HbA1c less than 7.4, 7.0 and 6.5% in all the participants tended to be higher in group D than in group N (p < 0.047 for 7.4%, but not significant for others). In conclusion, the early introduction of pharmacological monotherapy in addition to lifestyle intervention seem to suppress mild hyperglycemia with small doses of antihyperglycemic agents for 3 years, except for the use of SU drug. Although a larger scale of trial will be necessary to conclude, the early treatment with suitable monotherapy could be effective to bring and keep "safe level of glycemia".

Marked removal of bezafibrate-induced high-density lipoprotein-cholesterol by low-density lipoprotein apheresis.

BACKGROUND: A case of marked reduction of the bezafibrate-induced increase of high-density lipoprotein (HDL)-cholesterol by low-density lipoprotein apheresis (LDL-apheresis) has not been previously reported. METHODS: A 68-year-old Japanese man with arteriosclerosis obliterans (ASO), diabetes mellitus, and hyperlipidemia underwent LDL-apheresis, followed by the concomitant bezafibrate administration. Plasma lipids of pre- and post-LDL-apheresis were measured and apolipoprotein E (apoE) localization of the pre- and post-LDL-apheresis was detected by agarose gel electrophoresis. RESULTS: Plasma concentrations of the total cholesterol, LDL-cholesterol, triglyceride, and HDL-cholesterol of pre-LDL-apheresis were 4.78 +/- 0.36, 2.74 +/- 0.24, 2.44 +/- 0.52, and 0.92 +/- 0.10 mmol/l, respectively; those of the post-LDL-apheresis were 1.94 +/- 0.31, 0.72 +/- 0.13, 0.81 +/- 0.38, and 0.86 +/- 0.11 mmol/l, respectively. LDL-apheresis reduced HDL-cholesterol by 6.4% (p=0.346). During the bezafibrate administration, plasma concentrations of the above of pre-LDL-apheresis were 5.24 +/- 0.34, 3.28 +/- 0.22, 1.26 +/- 0.25, and 1.39 +/- 0.21 mmol/l, respectively; those of the post-LDL-apheresis were 2.25 +/- 0.44, 0.80 +/- 0.12, 0.58 +/- 0.19, and 1.18 +/- 0.16 mmol/l, respectively. LDL-apheresis reduced HDL-cholesterol by 15.2% (p<0.01). Plasma apolipoprotein E detected between the prebeta- and alpha-mobility was markedly lower after the LDL-apheresis in the agarose gel electrophoresis. CONCLUSIONS: The removal of the bezafibrate induced an increase of the HDL-cholesterol by LDL-apheresis.

Report of the Committee on the classification and diagnostic criteria of diabetes mellitus.

In 1995, the Japan Diabetes Society (JDS) appointed the Committee for the Classification and Diagnosis of Diabetes Mellitus. The Committee presented a final report in May 1999 in Japanese. This is the English version with minor modifications for readers outside Japan. CONCEPT OF DIABETES MELLITUS: Diabetes mellitus represents a group of diseases of heterogeneous etiology, characterized by chronic hyperglycemia and other metabolic abnormalities, which are due to deficiency of insulin effect. After a long duration of metabolic derangement, specific complications of diabetes (retinopathy, nephropathy, and neuropathy) may occur. Arteriosclerosis is also accelerated. Depending on the severity of the metabolic abnormality, diabetes may be asymptomatic, or may be associated with symptoms (thirst, polyuria, and weight loss), or may progress to ketoacidosis and coma. CLASSIFICATION: Both etiological classification and staging of pathophysiology by the degree of deficiency of insulin effect need to be considered. The etiological classification of diabetes and related disorders of glycemia includes, (1) type 1; (2) type 2; (3) those due to specific mechanisms and diseases; and (4) gestational diabetes mellitus. Type 1 is characterized by destructive lesions of pancreatic beta cells either by an autoimmune mechanism or of unknown cause. Type 2 diabetes is characterized by combinations of decreased insulin secretion and decreased insulin sensitivity (insulin resistance). Category (3) includes two subgroups; subgroup A is diabetes in which specific mutations have been identified as a cause of genetic susceptibility, while subgroup B is diabetes associated with other pathologic conditions or diseases. The staging of glucose metabolism includes normal, borderline and diabetic stages. The diabetic stage is further classified into three substages; non-insulin requiring, insulin-requiring for glycemic control, and insulin-dependent (ID) for survival. In each individual, these stages may vary according to the deterioration or the improvement of the metabolic state, either spontaneously or by treatment. DIAGNOSIS: The confirmation of chronic hyperglycemia is a prerequisite for the diagnosis of diabetes mellitus. The state of glycemia may be classified within three categories, diabetic type; borderline type; and normal type. Diabetic type is defined when fasting plasma glucose (FPG) is 7.0 mmol/l (126 mg/dl) or higher, and/or plasma glucose 2 h after 75 g glucose load (2hPG) is 11.1 mmol/l (200 mg/dl) or higher. A casual plasma glucose (PG) > or =11.1 mmol/l (200 mg/dl) also indicates diabetic type. Normal type is defined when FPG is below 6.1 mmol/l (110 mg/dl) and 2hPG below 7.8 mmol/l (140 mg/dl). Borderline type includes those who are neither diabetic nor normal types. These cutoff values are for venous PG measurements. The persistence of 'diabetic type' in a subject indicates that he or she has diabetes. For children, a dose of 1.75 g/kg (maximum, 75 g) is used for oral glucose tolerance test (OGTT). The procedure for clinical diagnosis is as follows. Diabetes mellitus is diagnosed when hyperglycemia meeting the criteria for 'diabetic type' is shown on two or more occasions examined on separate days. Diabetes can be diagnosed by a single PG test of 'diabetic type' if one of the following three conditions co-exists, (1) typical symptoms of diabetes mellitus; (2) HbA1c > or =6.5% by a standardized method; or (3) unequivocal diabetic retinopathy. If the above conditions ((1) or (2)) have been present in the past and well documented, the subject is diagnosed either to have diabetes or to be suspected of diabetes, even if the present level of glycemia does not reach that of 'diabetic type'. If the diagnosis of diabetes cannot be established by these procedures, re-testing of PG is recommended after an appropriate interval. The physician should assess not only the presence or absence of diabetes, but also its etiology and glycemic stage, and the presence and absence of diabetic complications or associated conditions. EPIDEMIOLOGICAL ASPECTS AND SCREENING: In order to determine the prevalence of diabetes in a population, 'diabetic type' may be regarded as 'diabetes'. The use of 2hPG cutoff level of > or =11.1 mmol/l (200 mg/dl) is recommended. If this is difficult, the FPG cutoff level of > or =7.0 mmol/l (126 mg/dl) can be used, but is likely to lead to under-ascertainment. For screening, the most important point is not to overlook 'diabetes'. In addition to parameters of hyperglycemia, clinical information such as family history, obesity etc., should be regarded as indications for further testing. NORMAL TYPE AND BORDERLINE: Only FPG and 2hPG are adopted as cutoff values, but in clinical situations, it is recommended to measure PG also at 30 and 60 min during 75 g OGTT. Among people with normal type, those with 1hPG higher than 10.0 mmol/l (180 mg/dl) are at higher risk to develop diabetes than those with lower 1hPG. When OGTT is performed, the borderline type corresponds to the sum of impaired fasting glycemia (IFG) plus impaired glucose tolerance (IGT) according to the new WHO report. Subjects in this category are at higher risk of developing diabetes than those with 'normal type'. Those with low insulinogenic index (the ratio of increment of plasma insulin to that of PG at 30 min during OGTT) are at particularly high risk to develop diabetes. Microvascular complications are rare but arteriosclerotic complications are fairly frequent in this category. GESTATIONAL DIABETES MELLITUS (GDM): The current definition of GDM is ' any glucose intolerance developed or detected during pregnancy'. We adopt the proposal of the Japan Society of Gynecology and Obstetrics for the diagnosis of GDM (1984). GDM is defined when two or more values during a 75 g OGTT are higher than the following cutoff levels; FPG > or =5.5 mmol/l (100 mg/dl), 1hPG > or =10.0 mmol/l (180 mg/dl) and 2hPG > or =8.3 mmol/l (150 mg/dl). As a screening test, subjects with casual PG > or =5.5 mmol/l (100 mg/dl) are recommended for further testing. Patients who have had documented glucose intolerance before pregnancy, and who present as 'diabetic type' should be under closer supervision than those who develop GDM during pregnancy for the first time. HbA1c: There is a large overlap in the distribution of HbA1c between groups with 'normal type' and 'borderline type' and mild 'diabetic type'. Therefore, HbA1c is not a suitable parameter to detect mild glucose intolerance. HbA1c higher than 6.5% suggests diabetes, but HbA1c below 6.5% alone should not be taken as evidence against the diagnosis of diabetes. COMPARISON WITH REPORTS OF AMERICAN DIABETES ASSOCIATION (ADA) IN 1997 AND WHO IN 1999: The present report is unique in the following points when compared with those of the ADA 'Diabetes Care 20 (1997) 1183' and WHO 'Report of a WHO Consultation (1999)'. (1) Diabetes due to specific mechanisms and diseases is divided into two subgroups; diabetes in which genetic susceptibility is clarified at the DNA level and diabetes associated with other diseases or conditions. (2) Cutoff PG levels are the same as those of ADA and WHO, but a term 'type' is added to each glycemic category, because a single coding of 'diabetic type' hyperglycemia does not define diabetes. Diabetes is diagnosed when 'diabetic type' hyperglycemia is shown on two or more occasions. (3) A single 'diabetic type' hyperglycemia is considered sufficient for the diagnosis of diabetes, if the patient has typical symptoms, HbA1c > or =6.5%, or diabetic retinopathy. (4) OGTT is recommended for those with mild hyperglycemia, because FPG criteria alone would overlook many subjects with 'diabetic type' in Japan. High 1hPG without elevation of FPG and 2hPG is also considered to be a risk factor for future diabetes. (5) Borderline type in the present report corresponds to the sum of IFG and IGT by WHO when OGTT is performed. (6) New criteria for GDM by OGTT are proposed.

Thiazolidinediones increase the number of platelets in immune thrombocytopenic purpura mice via inhibition of phagocytic activity of the reticulo-endothelial system.

Thiazolidinediones (TZDs) have broad spectrum of actions, including immunomodulating effects that are dependent or independent of the target nuclear receptor, peroxisome proliferator activated receptor-gamma (PPAR-gamma). In this study, we investigated the effect of TZDs on the platelet numbers in male immune thrombocytopenic purpura (ITP) model mice, (NZW x BXSB)F(1) (W/BF(1)) in vivo, and attempted to clarify the mechanism of action. Seven-day treatment with troglitazone increased platelet counts by 66% compared with those of controls. Within two weeks after the termination of the treatment period, the numbers of platelets were decreased to the level in controls. Pioglitazone showed only weak increasing effect on platelet counts in short-term experiment. However, long-term treatment with the drug resulted in a more pronounced up-regulation of platelets. We next assayed the platelet-associated antibodies (PAA) and the survival rate of antibody-sensitized mouse erythrocytes (Ab-mRBC) in W/BF1 mice. Pioglitazone slightly decreased the production of PAA and significantly elongated the survival period of Ab-mRBC in vivo. These drugs showed dose-dependent inhibitory effects on the cell proliferation and Fcgamma receptor (FcgammaR)-mediated phagocytic activity of macrophage-like cells in vitro. These results suggest that TZDs improve platelet counts in this mouse model mainly by suppressing systemic reticulo-endothelial phagocytic function.

Effects of long-term treatment with ranirestat, a potent aldose reductase inhibitor, on diabetic cataract and neuropathy in spontaneously diabetic torii rats.

We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0-6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P < 0.01). Ranirestat significantly (P < 0.01) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently (P < 0.01). Epalrestat also reversed the prevented MNCV decrease (P < 0.05). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, (P < 0.05, <0.01, and <0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only.

Fasting plasma glucose and incidence of diabetes --- implication for the threshold for impaired fasting glucose: results from the population-based Omiya MA cohort study.

AIM: In 2003, the American Diabetes Association recommended that the threshold for diagnosing impaired fasting glucose (IFG) should be lowered from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL). To discuss the diagnostic threshold for IFG, the association between fasting plasma glucose (FPG) and the risk of future diabetes must be known; however, data regarding this relation in the Japanese population are scarce. The aim of this study was to determine the relation between FPG and the risk of future diabetes in the Japanese general population. METHODS: A retrospective cohort study was conducted using data from annual health check-ups performed in Omiya city. A total of 11,369 subjects between the ages of 40-79 years who were not diabetic at baseline were followed for seven years. Diabetes was defined as FPG > or =126 mg/dL or self-report. RESULTS: The incidence of diabetes increased as the baseline FPG level increased and a similar pattern was observed irrespective of sex or age. The hazard ratios compared with subjects with FPG <85 mg/ dL adjusted for possible confounding factors were 3.83 (95% confidence interval (95% CI); 2.41-6.08) for subjects with 100 to 104 mg/dL FPG and 7.87 [corrected] (95% CI; 4.98-12.4) for subjects with 105 to 109 mg/dL FPG. CONCLUSIONS: Subjects with 100-109 mg/dL FPG have an appreciable risk of diabetes that cannot be considered as "normal" and should be notified of their potential risk of developing diabetes.

Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy.

PURPOSE: We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy. METHODS: Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues. RESULTS: The mean VEGF and AGE levels in the vitreous (695.7pg/ml and 2.4mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9pg/ml, p=0.0007 and 1.3mg/ml, p=0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly (r=0.6; p=0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes. CONCLUSIONS: By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina.

Characteristics of diabetic retinopathy in SDT rats.

BACKGROUND: We previously reported a new diabetic strain of the Sprague-Dawley rat, named the Spontaneously Diabetic Torii (SDT) rat. The purpose of the present study was to report the histologic and ultrastructural characteristics of diabetic retinopathy (DR) in a new animal model, the SDT rat. METHODS: Fifty-three eyes of 43 SDT rats of various ages (35-82 weeks) were examined, of which 33 underwent histopathologic examination, 15 eyes fluorescein-dextran microscopy, and five eyes the trypsin digestion method. RESULTS: Of the 33 eyes examined histopathologically, DR was identified in 20 eyes (61%). Large retinal folds mimicking diabetic tractional retinal detachment were observed in 20 eyes (61%). Retinal hemorrhages were seen in four eyes (12%). A neovascular fibrous membrane around the iris developed in five eyes (15%), of which two eyes had a massive anterior chamber hemorrhage. Of the 15 eyes examined by fluorescein-dextran microscopy, an area of nonperfusion and/or extensive hyperfluorescence was observed in 12 eyes (80%). Of the five eyes examined using the trypsin digestion method, acellular capillaries and pericyte loss were observed in four eyes (80%). Of the 53 eyes, the previously mentioned retinal changes of DR were observed in 36 eyes (68%). The rats with DR (49-82 weeks; mean, 60 weeks) were older than the rats without DR (35-55 weeks; mean, 40 weeks) (p < 0.001). CONCLUSION: Large retinal folds mimicking tractional retinal detachment with extensive leakage of fluorescein around the optic disk was the most prominent finding of DR in SDT rats.

Glucose intolerance and hyperlipidemia prior to diabetes onset in female Spontaneously Diabetic Torii (SDT) rats.

The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P < 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes.

Chronological characterization of diabetes development in male Spontaneously Diabetic Torii rats.

To characterize the underlying mechanisms of diabetes development in males of the Spontaneously Diabetic Torii (SDT) rat, a novel spontaneous model for diabetes, we chronologically examined them, focusing on their diabetic features and the pathological changes in the pancreatic islets. Male SDT rats exhibited glucose intolerance with impaired insulin secretion after 14 weeks and developed diabetes with remarkable hyperglycemia and marked hypoinsulinemia after 20 weeks. At prediabetic stage (10-20 weeks), they were normoglycemic, but had significantly lower insulin levels of plasma and pancreas than the normal rats. Their beta-cell volume was already smaller significantly at 10 weeks than that of normal rats. The primary changes of the pancreatic islets were microvascular events such as congestion and hemorrhage at 8-10 weeks. Thereafter, the SDT rat islets were affected with inflammation and progressive fibrosis (at 10-20 weeks), and eventually atrophied with a loss of beta-cells (at 38 weeks). These results indicate that the male SDT rats develop spontaneous diabetes with an absolute decrease in the insulin secretory capacity of the islets.