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Aim Primary aldosteronism, which is usually caused by an aldosterone-producing tumour, affects glucose metabolism. The effects of this condition on insulin secretion and insulin sensitivity have remained unclear, however. To gain insight into the influence of primary aldosteronism on glucose tolerance, various parameters related to insulin secretion or insulin sensitivity in patients with an aldosterone-producing tumour were comprehensively analyzed. Methods To assess 14 patients with an aldosterone-producing tumour, hyperglycaemic and hyperinsulinaemic–euglycaemic clamp tests as well as oral glucose tolerance tests (OGTTs) were performed before and after tumour excision. Time between presurgical analysis and surgery was 27–559 (194 ± 132) days, and 14–142 (51 ± 38) days between surgery and postsurgical analysis. Various parameters related to insulin secretion or sensitivity as determined by OGTT as well as hyperglycaemic and hyperinsulinaemic–euglycaemic clamp analyses were evaluated. Results Surgical treatment of tumours ameliorated hypokalaemia and reduced plasma aldosterone levels. First and second phases of insulin secretion during the hyperglycaemic clamp, as well as the insulinogenic index and total insulin secretion measured during OGTT, were also improved after surgery. In addition, the insulin sensitivity index determined during the hyperinsulinaemic–euglycaemic clamp was reduced after surgery. Conclusion Primary aldosteronism impairs insulin secretion.

Fulminant type 1 diabetes mellitus (FT1DM), characterized by rapid and almost complete destruction of pancreatic β-cells, is a newly identified subtype of type 1 diabetes mellitus. Although, the pathophysiology of this condition remains still unclear, histological evidence suggests that not only β-cells but also α-cells of pancreatic islets are reduced in number in FT1DM. However, the ability of glucagon secretion in patients with this condition has remained largely uncharacterized. We therefore examined glucagon secretion in patients with FT1DM and compared that with patients with other types of diabetes mellitus. Fasting glucagon levels as well as glucagon secretion induced by intravenous administration of arginine were measured in hospitalized 83 patients with diabetes mellitus, including 4 with FT1DM, 18 with type 1 diabetes mellitus (T1DM), 40 with type 2 diabetes mellitus (T2DM), 5 with slowly progressive insulin-dependent diabetes mellitus (SPIDDM), and 16 with pancreatic diabetes mellitus (PDM). The area under the curve for serum glucagon levels after arginine infusion in FT1DM patients was significantly smaller than that in T1DM, T2DM, or SPIDDM patients but was similar to that in PDM patients. The fasting serum glucagon level of FT1DM patients was lower than that of T1DM or T2DM patients but did not significantly differ from that of SPIDDM or PDM patients. These results suggest that glucagon secretion is impaired in patients with FT1DM.

Aims/introduction Whereas some clinical studies have shown that excessive fat accumulation in the pancreas is associated with impairment of insulin secretion, others have not found such an association. 1 H magnetic resonance spectroscopy allows quantitative fat analysis in various tissues including the pancreas. The pathological relevance of pancreatic fat content (PFC) in Japanese individuals remains unclear, however. Materials and methods We analyzed PFC in 30 Japanese individuals with normal glucose tolerance by 1 H magnetic resonance spectroscopy, and then investigated the relationships between PFC and indexes of insulin secretion and insulin sensitivity-resistance determined by an oral glucose tolerance test. We also measured hepatic fat content and intramyocellular lipid content by 1 H magnetic resonance spectroscopy, as well as visceral fat area and subcutaneous fat area by magnetic resonance imaging, and we examined the relationships between these fat content measures and oral glucose tolerance test-derived parameters. Results PFC was correlated with indexes of insulin sensitivity-resistance, but not with those of insulin secretion. Hepatic fat content and visceral fat area were correlated with similar sets of parameters as was PFC, whereas subcutaneous fat area was correlated with parameters of insulin secretion, and intramyocellular lipid content was not correlated with any of the measured parameters. The correlation between PFC and homeostasis model assessment of insulin resistance remained significant after adjustment for age, body mass index and sex. Among fat content measures, PFC was most highly correlated with hepatic fat content and visceral fat area. Conclusions PFC was correlated with indexes of insulin resistance, but not with those of insulin secretion in non-obese Japanese individuals with normal glucose tolerance.

Context:Pheochromocytoma and paraganglioma are catecholamine-producing tumors that oftenimpair glucose tolerance. The effects of these tumors on insulin sensitivity and insulin secretion inpatients have remained unclear, however.Objective:To characterize the influence of pheochromocytoma or paraganglioma on glucosetolerance, we comprehensively analyzed various parameters related to insulin secretion or insulinsensitivity in patients with these tumors.Design:Hyperglycemic and hyperinsulinemic-euglycemic clamps, as well as an oral glucose tolerancetest (OGTT), were performed in patients before and after tumor excision.Setting:Patients underwent metabolic analyses on admission to Kobe University Hospital.Patients:Eleven patients with pheochromocytoma and two with paraganglioma were examined.Intervention:None.Main Outcome Measures:We evaluated various parameters related to insulin secretion or insulinsensitivity as determined by an OGTT and by hyperglycemic and hyperinsulinemic-euglycemicclamp analyses.Results:Surgical treatment of the tumor reduced urinary catecholamine excretion and improvedglucose tolerance. The insulinogenic index, but not total insulin secretion, measured during theOGTT as well as the first phase, but not the second phase, of insulin secretion during the hyper-glycemic clamp were improved after surgery. The insulin sensitivity index determined during thehyperinsulinemic-euglycemic clamp remained unchanged after surgery.Conclusion:These results suggest pheochromocytoma and paraganglioma impair glucose toleranceprimarily through impairment of insulin secretion—in particular, that of the early phase of theinsulin secretory response. A prospective study with more patients is warranted to further confirmthese results.(J Clin Endocrinol Metab102: 3400–3405, 2017)

Aims/hypothesis We compared the effects of insulin degludec (IDeg; Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin) and insulin glargine (IGlar; A21Gly,B31Arg,B32Arg human insulin) on the day-to-day variability of fasting plasma glucose (FPG) levels in individuals with type 1 diabetes treated with basal-bolus insulin injections. Methods The effects of basal-bolus insulin therapy for 4 weeks with either IDeg or IGlar as the basal insulin in adult C-peptide-negative outpatients with type 1 diabetes were investigated in an open-label, multicentre, randomised, crossover trial. Randomisation was conducted using a centralised allocation process. The primary endpoints were the SD and CV of FPG during the final week of each treatment period. Secondary endpoints included serum glycoalbumin level, daily dose of insulin, intraday glycaemic variability and frequency of severe hypoglycaemia. Results Thirty-six randomised participants (17 in the IDeg/IGlar and 19 in the IGlar/IDeg groups) were recruited, and data for 32 participants who completed the trial were analysed. The mean (7.74 ± 1.76 vs 8.56 ± 2.06 mmol/l; p = 0.04) and SD (2.60 ± 0.97 vs 3.19 ± 1.36 mmol/l; p = 0.03) of FPG were lower during IDeg treatment than during IGlar treatment, whereas the CV did not differ between the two treatments. The dose of IDeg was smaller than that of IGlar (11.0 ± 5.2 vs 11.8 ± 5.6 U/day; p

Objective The C-peptide index (CPI), a ratio of serum C-peptide to plasma glucose levels, is a readily measured index of β-cell function. The difference in the physiological features reflected by the index measured under fasting (F-CPI) or postprandial (PP-CPI) conditions has remained unclear, however. Materials/Methods We investigated the relationship of the two CPIs to indexes of insulin secretion measured with an oral glucose tolerance test (OGTT) or with hyperglycemic and hyperinsulinemic–euglycemic clamp analyses as well as to disposition indexes (indexes of insulin secretion adjusted for insulin sensitivity) calculated from OGTT- or clamp-based analyses. We also examined the relationship between glucose tolerance and the clamp-based disposition index. Results The clamp-based disposition index declined progressively from normal glucose tolerance to impaired glucose tolerance to Type 2 diabetes, and it strongly correlated with the 2-h plasma glucose level during an OGTT. For patients with Type 2 diabetes, both F-CPI and PP-CPI correlated with indexes of insulin secretion including HOMA-β, the insulinogenic index, the ratio of the area under the insulin curve to that under the glucose curve during an OGTT, the serum C-peptide level after glucagon challenge, as well as early and total insulin secretion measured with a hyperglycemic clamp. PP-CPI, but not F-CPI, was significantly correlated with clamp-based and OGTT-based disposition indexes. Conclusions F-CPI was correlated only with unadjusted indexes of insulin secretion, whereas PP-CPI was correlated with such indexes as well as with those adjusted for insulin sensitivity. The better clinical utility of PP-CPI might be attributable to these physiological characteristics.

We evaluated age-dependent changes in β-cell function as assessed with an oral glucose tolerance test (OGTT)-based analog of the disposition index (oral disposition index). A total of 110 Japanese normoglycemic subjects (aged 22-59 years) was divided into decadal age groups (20, 30, 40 and 50 s) and subjected to an OGTT. The oral disposition index was calculated as the product of the Matsuda index and the ratio of the area under the insulin curve to the area under the glucose curve for 0-120 min during the OGTT (AUCins/gluc120). Although indexes of insulin secretion, including AUCins/gluc120 and the insulinogenic index, did not differ among age groups, the oral disposition index differed significantly among decadal ages and declined with age. The oral disposition index is thus a sensitive measure of β-cell function, and a natural decline in such function likely begins in early adulthood and progresses with age. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00099.x, 2011).

The radioimmunoassay (RIA) for trypsin-like immunoreactivity (TLI) is one of the most sensitive and specific tests for detecting exocrine pancreatic insufficiency (EPI). An abnormally low serum TLI concentration (2.5 ng/ml) indicates end-stage EPI. Although RIA methods can be used to detect canine serum TLI, these procedures are beyond the capabilities of most veterinary clinics and general laboratories. Using monoclonal antibodies (mAbs), we developed an enzyme-linked immunosorbent assay (ELISA) for canine TLI and incorporated it into an immunochromatographic test (ICT) for the diagnosis of EPI. The ELISA was linear over TLI concentrations of 1-100 ng/ml. Levels of intra-assay coefficients of variance (CVs) were 1.8-6.1%, inter-assay CVs were 5.1-9.8%, and the recovery of TLI added to two samples of canine serum ranged from 89 to 111 and 93 to 108%, respectively. Good correlation (correlation coefficient, 0.974) occurred between the TLI values obtained by the ELISA method and those by RIA from 56 clinical samples. Serum TLI values in clinically healthy dogs ranged from 7.8 to 29.2 ng/ml by ELISA, and those from dogs with EPI were 0.0-0.6 ng/ml. The values were 0.0-287.4 ng/ml for dogs with pancreatitis, and those from dogs with gastrointestinal disease were 5.5-58.9 ng/ml. The only statistically significant difference (P0.01) occurred between the TLI level of healthy dogs and those with EPI. The ICT kit showed high reproducibility, and the TLI values yielding negative results differed significantly (P0.01) from those returning positive results. The ICT kit yielded negative results (indicating EPI) from clinical serum samples with TLI concentrations of 0.0-4.1 ng/ml by ELISA. Both the ELISA and ICT kit are useful tools in the diagnosis of canine EPI.

Evaluating insulin secretion ability and sensitivity is essential to establish an appropriate treatment for patients with type 2 diabetes. The serum C-peptide response (CPR) level is used to evaluate the quantity of endogenous insulin secretion. However, the serum CPR level alone cannot indicate insulin-secretion ability or insulin sensitivity, because plasma glucose levels influence endogenous insulin secretion and vice versa. The CPR index, a ratio of serum CPR level to plasma glucose concentration when measured simultaneously, was previously reported to be a useful marker to determine the necessity of insulin treatment in patients with type 2 diabetes, but the reasons are unknown. The aim of this study was to clarify which factors affect the CPR index in patients with type 2 diabetes. Totally, 121 subjects were included in this study; all participants were hospitalized for type 2 diabetes. On the day after admission, we calculated the CPR index from each patient's fasting blood sample and a blood sample taken 2 hours after breakfast (the postprandial sample). A detailed medical history was taken from each patient to establish the disease duration. The degree of diabetic retinopathy judged by an ophthalmologist was obtained from patients' medical records. An oral glucose tolerance test and a glucagon load test were performed after the fasting plasma glucose level decreased to 130 mg/dl, and indices of insulin secretion and sensitivity were calculated. Fasting and postprandial CPR indices were moderately correlated with total endogenous insulin secretion after oral glucose load and with the CPR level after glucagon load, insulin sensitivity, composite index, and the reciprocal index of homeostasis model assessment (HOMA-R-1). Furthermore, there was a weak but significant correlation between the postprandial CPR index and the duration of diabetes. The postprandial CPR index was inversely correlated with the degree of diabetic retinopathy, which is known to be associated with the duration of hyperglycemia. Our data clearly shows that the CPR index is a useful parameter to reflect the degree of impaired glucose tolerance.

We developed a one-step immunochromatography assay kit to measure high levels of canine trypsin-like immunoreactivity (cTLI) for bedside estimation of canine pancreatitis. The serum cTLI level can be determined within 10 min by visual comparison of color strengths in the test and reference zones. The serum cTLI levels determined by this method correlate well with canine TLI-ELISA and can be classified into 3 categories: cTLI levels higher than 60 ng/ml were considered positive; 20-60 ng/ml, weakly positive; and less than 20 ng/ml, negative. Twelve dogs suspected of pancreatitis were examined using this method; 4 dogs were positive, 2 were weakly positive, and 6 were negative. This test can detect a high level of serum cTLI and a positive result in the TLIH test will provide critical information for evaluation of pancreatitis in dogs.

Canine cationic trypsin was purified by salting-out, gel filtration and affinity chromatography. Purity was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weight was ca. 28kDa by SDS-PAGE. Thirty hybridomas were obtained which produced mAb to canine cationic trypsin by the cell fusion technique. Twenty-two of these recognized cationic trypsin only, while eight hybridomas recognized both cationic and anionic trypsin. Several of the anti-canine cationic trypsin mAb were purified by salting-out and DEAE ion-change chromatography using ascites fluid of immunized BALB/c mice. The mAb proved to have very high specificity to canine cationic trypsin as shown by immunoblotting and it may be possible to use them to develop clinical assays.

Insulin autoimmune syndrome, a relatively rare cause of hypoglycemia, is characterized by the production of autoantibodies to insulin in individuals who have not previously been injected with this hormone (1). Drug-induced autoimmunity appears to be important in the pathogenesis of this syndrome, given that ∼50% of affected individuals have taken certain drugs, most of which (such as methimazole, α-mercaptopropionyl glycine, or glutathione) contain the sulfydryl group, before its onset (1). We now report a case of insulin autoimmune syndrome likely induced by α-lipoic acid (ALA), a reduced form of which contains the sulfydryl group (2). A 32-year-old Japanese woman visited Ishida Clinic on 1 June 2005 because of a feeling of weariness before lunch and dinner. This symptom, which first occurred on 23 May 2005, was relieved by ingestion of the meal. The patient had been well until the onset of the preprandial weariness, had never been injected with insulin, and had no family history of metabolic, hormonal, or autoimmune diseases. Her weight was 60 kg and height 155.4 cm. The patient's plasma glucose levels during a 75-g oral glucose tolerance test (OGTT) (59, 154, 207, and 227 mg/dl at 0, 30, 60, and 120 min after glucose ingestion, respectively) performed on 3 June 2005 were consistent with a diagnosis of diabetes, whereas her A1C level was low (4.5%). Serum …

This is the first full report on the genetic linkage between Japanese Huntington's disease and the DNA markers D4S10 and D4S43/S127. With use of the HindIII, BglI, and EcoRI polymorphisms detected at D4S10, and the combination of all these polymorphisms to give composite haplotypes, nine Japanese Huntington's disease families were found to be informative. Three recombinants for D4S10 were detected in these families, giving a maximum lod score of 1.662 at a theta of 0.10. Similarly, when we used the MspI and PvuII polymorphisms detected by D4S43/S127, five families gave informative results. No recombinant was detected in these families, giving a maximum lod score of 3.348 at a theta of 0.00. These results clearly support the view that the Japanese Huntington's disease gene may be identical with the Western gene, in spite of the lower prevalence rate in Japan.

A 30-year-old male with manic-depressive psychosis took in 30ml of undiluted Smithion to commit suicide. Ten hours or so later, he was found in state of subconsciousness and admitted into our hospital.1. From the initial trance, he fell into a twilight state. After suffering from an amnestic syndrome and encountering difficulties in concentrating his attention, he was found in a depressive state on the 18th day. This depressive state was presumably a recurrence of the depression with which he had once suffered and therefore proved different from the depressive state unique to organophosphate poisoning.2. In respect to the psychatric symptoms caused by acute and subacute organophosphate poisoning and its sequela, a study is made on the basis of literature to make some comment.3. After a clinical course of two-and-a-half years, it was found that there were a slight degree of disturbance to registration and a drop in mental capacity. These were considered sequelas. These symptoms would not hamper his everyday life, but there were signs of a rise in the sense of quilty conscience and misery when he was in a depressive state.4. EEG indicates that the waves were slowing and paroxismal or sporadic small spikes. Two years later, EEG-findings were slightly abnormal with many sporadic slow α waves. No abnormalities were observed in computerized tomogram.

The authors administered 50-100 micrograms of thyroxine (T4) alone for 2 weeks to 20 patients with primary major depressive disorders, evaluated clinical changes, and compared the thyroid functions before and after the trial. The results showed a significant decrease in the Hamilton Rating Scale scores, and the efficacy of thyroid hormone alone was demonstrated against depression. It was also shown that this antidepressive effect varied widely from marked improvement to mild aggravation. The degree of clinical improvement had no significant relationship with sex, age, subtype of depression, and severity of symptoms before treatment. But it had significant positive correlations with the pre-trial T3, T4, T3 uptake, free T4 index and BMR. That is, patients with a higher pre-trial thyroid function showed a greater improvement. Thus, it was suggested that the antidepressive effects is closely associated with the mechanism which suppresses endogenous thyroid hormones.