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Recently, oral hypoglycemic agents with newer glucose lowering mechanisms have been on release. This is mostly to meet the diabetic patient’s need to avoid hypoglycemia, which is profoundly important for better long-term outcome of the treatment. In this study, we quantified the annual number of patients with type 2 diabetes who experienced hypoglycemia needing the third-party assistance who had random sample plasma glucose

The trajectory of glomerular filtration rate (GFR) in relation to glomerular hyperfiltration (GHF) has been unknown. It was evaluated retrospectively in 23,982 GHF-free health examinees who were followed for 2−10 yr (mean: 5.1 yr). GFR was estimated by the serum creatinine concentration, and GHF was defined as age- and sex-specific estimated GFR (eGFR) ≥ 95% of the Japanese general population. The temporal profile of eGFR was plotted in a GHF-centered way, which was fitted to a random coefficient linear mixed model. Of the 23,982 subjects, 797 and 23,185 subjects developed or did not develop GHF, respectively, so that they were termed as the GHF(+)and GHF(−)groups. At baseline, median eGFR was significantly elevated in the GHF(+)group compared with in the GHF(−)group: 94.1 versus 77.3 mL/min/1.73 m2( P < 0.001). Elevation of basal eGFR lasted for a mean (SD) of 3.3 (1.9) yr in the GHF(+)group; mean eGFR then rose to the GHF range, which was 108.5 mL/min/1.73 m2. The eGFR decline after the peak was steeper in the GHF(+)group than in the GHF(−)group: −0.984 versus −0.497 mL/min/1.73 m2/yr ( P < 0.001). Baseline eGFR, but no other variable, well predicted incident GHF, with an area under the receiver operating characteristic curve of 0.87 (95% confidence interval: 0.86–0.88). In conclusion, GHF occurs as a chronic, multiphasic phenomenon: initially with a sustained GFR elevation for years, followed by a GFR surge to the GHF range, which was accompanied by accelerated GFR declining.

A 59-year-old woman unaware of having diabetes was transferred due to coma. Upon discovery at home, her consciousness on the Glasgow Coma Scale was E1V2M4, BP 95/84 mmHg, body temperature 34.7°C. On arrival at ER, height was 1.63 m, weight 97 kg, plasma glucose (PG) 1,897 mg/dL, HbA1c 13.6%, osmolality 421 mosm/kg, arterial pH 7.185, lactate 6.34 mmol/L, β-hydroxybutyrate 7.93 mmol/L. With saline and regular insulin infusion, PG was lowered to 1,440 mg/dL at 2 hours and then to 250 mg/dL by Day 3, and consciousness normalized by Day 5. On admission, serum immunoreactive insulin (IRI) was undetectable (

SARS-CoV-2 infection (COVID-19) is currently a tremendous global health problem. COVID-19 causes considerable damage to a wide range of vital organs most prominently the respiratory system. Recently, clinical evidence for thyroidal insults during and after COVID-19 has been accumulated. As of today, almost all non-neoplastic thyroid diseases, i.e., Graves’ disease, Hashimoto’s thyroiditis, subacute, painless and postpartum thyroiditis, have been reported as a complication of COVID-19, and causality by the virus has been strongly implicated in all of them. Similar thyroid problems have been reported in the past with the SARS-CoV outbreak in 2002. In this review, we briefly look back at the reported evidence of alteration in thyroid functionality and thyroid diseases associated with SARS-CoV and then proceed to examine the issue with COVID-19 in detail, which is then followed by an in-depth discussion regarding a pathogenetic link between Coronavirus infection and thyroid disease.

Aims To compare impact of elevated HbA1c and fasting plasma glucose (FPG) on incident chronic kidney disease (CKD) in a non-diabetic cohort. Methods Data from diabetes- and CKD-free 25,109 health examinees were retrospectively analysed with a mean observation period of 5.3 years. Prediabetes was diagnosed by the ADA and WHO criteria, and CKD by estimated glomerular filtration rate (eGFR) Results For incident CKD (n = 2483), high HbA1c but not FPG was an independent risk: adjusted hazard ratio (AHR, 95%CI) for HbA1c 1% and FPG 1 mmol/L, 1.91 (1.70–2.16) and 0.85 (0.60–1.20), respectively. Prediabetes by the ADA and WHO criteria were both risk for CKD with AHR (95%CI), 1.21 (1.12–1.32) and 1.31 (1.16–1.48), respectively. Prediabetes diagnosed by ‘elevated HbA1c irrespective of FPG’, either by the ADA and the WHO definition, was a risk with AHR (95%CI), 1.48 (1.36–1.61) and 1.51 (1.31–1.74), respectively. In contrast, prediabetes diagnosed by ‘raised FPG irrespective of HbA1c’ was not a CKD risk. Conclusions Elevated HbA1c, but not FPG, identified CKD risk in non-diabetic individuals.

A hypothesis that postchallenge hyperglycemia in subjects with low body weight (BW) may be due, in part, to small glucose volume (GV) was tested. We studied 11,411 nondiabetic subjects with a mean BW of 63.3 kg; 5,282 of them were followed for a mean of 5.3 yr. In another group of 1,537 nondiabetic subjects, insulin sensitivity, secretion, and a product of the two (index of whole body insulin action) were determined. Corrected 2 h-plasma glucose (2hPGcorr) during a 75-g oral glucose tolerance test in subjects with BW ≤ 59 kg was calculated as 2hPGcorr = δPG2h · ECW/[16.1 (males) or 15.3 (females)] + fasting PG (FPG), where δPG2h is plasma glucose increment in 2 h; ECW is extracellular water (surrogate of GV); FPG is fasting plasma glucose; and 16.1 and 15.3 are ECW of men and women, respectively, with BW = 59 kg. Multivariate analyses for BW with adjustment for age, sex, and percent body fat were undertaken. BW was, across its entire range, positively correlated with FPG ( P < 0.01). Whereas BW was correlated with 2hPG and δPG in a skewed J-shape, with inflections at around 60 kg ( P for nonlinearity < 0.01 for each). Nonetheless, in those with BW ≤ 59 kg, insulin sensitivity, secretion, and action were unattenuated, and incident diabetes was less compared with heavier counterparts. BW was linearly correlated with 2hPGcorr, i.e., the J-shape correlation was mitigated by the correction. In conclusion, postchallenge hyperglycemia in low BW subjects is in part due to small GV rather than impaired glucose metabolism.

The quantitative impact of weight gain on prediabetic glucose dysregulation remains unknown; only one study quantitated the impact of weight loss. We quantified the impact of weight gain on the evolution and regression of prediabetes (PDM).In 4234 subjects without diabetes, using logistic regression analysis with a 4.8-year follow-up period, we analyzed the relationship between (1) δBMI (BMIMean (±s.d.) δBMI was 0.17 (±1.3) kg/mIn Japanese adults, an increase in the BMI by even 1 kg/m

Aims/Introduction ‘The Standard Diabetes Manual’ has been developed by clinical researchers from multiple major institutions in Japan, such as the National Center for Global Health and Medicine, as a comprehensive disease management program, including collaboration between primary care physicians (PCPs) and specialist services. The present study evaluated the efficacy of the manual as a quality improvement strategy in diabetes care by PCPs. Materials and Methods A total of 42 PCPs in eight domestic districts of the Japan Medical Association were allocated to either the intervention group or the control group in a cluster‐randomized design. The PCPs in both groups were provided with a copy of the Diabetes Treatment Guide published by the Japan Diabetes Society, and the PCPs in the intervention group additionally received a copy of the manual and a 30‐min relevant seminar at the inception of the intervention. The primary end‐point was the adherence to the following performances as quality indicators: evaluation of retinopathy, and urinary albumin excretion measurements and serum creatinine measurements, as recommended by the Japan Medical Association. Results A total of 416 patients were enrolled by 36 PCPs. During the 1‐year follow‐up period, the proportion of PCPs who adhered to recommendation‐concordant measurements of urinary albumin excretion was significantly higher in the intervention group than in the control group (adherence: 17.9% vs 5.3%, P = 0.016). The other parameters were not statistically different between the two groups. Conclusions Implementation of ‘The Standard Diabetes Manual’ potentially leads to an improved quality of diabetes management by PCPs.

A 43-yr-old hypertensive male was admitted due to hypokalemia (1.8 mEq/L) and renal dysfunction (eGFR, 20.0 mL/min/1.73 m2). His plasma aldosterone was 901.0 ng/dL, plasma renin activity 5.7 ng/mL/hr, and aldosterone/renin activity ratio 158. Angiotensin II (AII) was 0.7 pg/mL, ACTH

To clarify if prediabetes defined by the International Expert Committee (PrediabetesIEC) and/or the American Diabetes Society (PrediabetesADA) is a risk for incident glomerular hyperfiltration (GH). 24,524 health examinees without diabetes, chronic kidney disease (CKD), GH and antihypertensive treatment at baseline, and repeated examinations at least twice during a mean of 5.3 years were retrospectively analysed. Diabetes was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L and/or HbA1c ≥ 47 mmol/mol, CKD by estimated glomerular filtration rate (eGFR)

Long-term glucose supplementation is required to prevent hypoglycemia after massive insulin overdosing. We fitted the blood insulin concentration-time profile to the model: I = A·exp(-a·t) + B·exp(-b·t), where I (μU/mL) is the serum/plasma insulin concentration, A (μU/mL) and B (μU/mL) are the peak insulin concentrations of each component, a (time-1) and b (time-1) are the time constants of each component, and t (h) is the time elapsed from the peak of blood insulin level. Additional components were considered as needed. Patient 1 had auto-injected 600 U NovoRapid® 30Mix, and Patient 2 had auto-injected 300 U Novolet®R (regular) and 1,800 U NovoLet®N (NPH). We used the disappearance of therapeutic doses of the respective insulin in healthy individuals as controls, and we obtained parameters by Excel solver. In Patient 1, the parameter values were A = 1490.04 and a = 0.15 for insulin aspart and B = 60.66 and b = 0.04 for protaminated aspart. In Patient 2, the values were A = 784.45 and a = 0.38 for regular insulin and B = 395.84 and b = 0.03 for NPH. Compared with controls, the half-lives (t1/2) for insulin aspart and protaminated aspart were 4 and 2 times longer, respectively, in Patient 1. In Patient 2, the t1/2 for regular and NPH insulin were 2 and 7 times longer than those in the controls, respectively. In conclusion, the t1/2 for insulin was elongated 2 to 7 times after massive overdosing, explaining why glucose supplementation is needed for long periods in these cases.

It has been unknown if attenuated insulin sensitivity (Si) in non-alcoholic fatty liver disease (NAFLD) is a cause or a result. We examined the impact of attenuated Si on NAFLD evolution. We observed 4856 NAFLD- and diabetes-free participants for a mean 2.9 years. Si was indexed by single point insulin sensitivity estimator (SPISE = [600 × HDL-c0.185]/[TG0.2 × BMI1.338]), correlating with 1/HOMA-IR in an independent cohort (n = 1537, Spearman rho = 0.519, P 10.06) as the reference, tertile 1 (

The impact of postchallenge glucose on the relationship between insulin sensitivity (SI) and secretion (β) is unknown. We analyzed data from 2,264 health examinees (male/female 1,524/740, median age 54 yrs) with normal glucose tolerance (NGT, n = 1,623), non-diabetic hyperglycemia (NDH, n = 555), or diabetes (DM, n = 86) using OGTT-derived indices of SI (insulin sensitivity index [ISI]-Matsuda, 1/HOMA-IR, and 1/fasting IRI) and β (δIRI0-30/δPG0-30, and Stumvoll 1st [Stumvoll-1] and 2nd [Stumvoll-2] phases). The combination of 1/HOMA-IR and Stumvoll-1 recapitulated the hyperbolic SI-β relationship with the slope of the fitted line -1.000 in NGT subjects, and therefore it was utilized in the following analysis of the SI-β correlation. In multiple regression analysis of the relationship between SI and β, an independent correlation was found for 1 h-plasma glucose (PG; PG60) but not for 2 h-PG. When the NGT subjects were grouped by PG60 quartile (Q), the fitted line was flat in Q1 but progressively steeper from Q2 to Q4, with a slope (95%CI) of -0.663 (-0.726~-0.605), -0.680 (-0.745~-0.622), -0.847 (-0.922~-0.779), and -1.259 (-1.370~-1.158) (P for trend < 0.05). The fitted line steepened further in the NDH and DM groups, with a slope of -1.545 and -1.915, respectively (P < 0.01 for the difference). The intercept of the fitted line for SI-β correlation was also progressively lower across the PG60 Q for NGT, NDH, and DM. In conclusion, using the 1/HOMA-IR-Stumvoll-1 pair for an analysis of the SI-β relationship, elevated PG60 was associated with steepening and downward shifting of the fitted line for the SI-β correlation. The finding suggests impaired beta cell function.

Although accelerated β-cell telomere shortening may be associated with diabetes that shows a dramatically increased incidence with aging, β-cell telomere length in diabetes has never been explored.The objective of the present study was to examine telomere length in the β-cells of patients with diabetes.We determined telomere length in β- and α-cells of pancreases obtained at autopsy from 47 patients with type 2 diabetes and 51 controls, all older than 60 years.The normalized telomere to centromere ratio (NTCR), an index of telomere length, was determined for β- (NTCRβ) and α- (NTCRα) cells by quantitative fluorescence in situ hybridization.The NTCRβ was reduced by 27% ± 25% and NTCRα by 15% ± 27% in the patients with diabetes relative to the controls (P.01 for both). Importantly, the degree of shortening was significantly (P.01) greater in β-cells than in α-cells. The histogram of NTCR distribution was significantly skewed to the left in the patients with diabetes relative to the controls for both β- and α-cells, indicating preferential depletion of longer-telomere islet cells. Glycated hemoglobin was negatively correlated with β-cell telomere length, and the telomeres were significantly shorter in patients who had used hypoglycemic agents than in those who had not.The telomeres of β-cells are shortened in patients with type 2 diabetes. There may be a vicious cycle involving β-cell telomere attrition and sustained hyperglycemia.

The population attributable fraction (PAF) of risk factors for the worsening of glucose metabolism in subjects with normal glucose tolerance (NGT) has not been calculated. Our aim was to obtain the PAF of increased body mass index (BMI) and attenuated beta-cell function (BCF) on worsening of glucose metabolism in subjects with NGT. We longitudinally analyzed 604 Japanese adults. The follow-up glucose tolerance status was determined 3.7 years later: 430 participants remained in the NGT category and 102 had progressed to impaired fasting glucose, 67 to impaired glucose tolerance, and 5 to diabetes mellitus. A product of ISIMatsuda and Stumvoll-1, i.e., oral disposition index (DIO), was used as a measure of BCF. The optimal cutoff baseline BMI and DIO values for the prediction of the worsening of glucose metabolism were 23.1 and 7.299 kg/m(2), respectively. Isolated increased BMI (iBMIHIGH), isolated low DI (iDIOLOW), and "BMIHIGH and DIOLOW (BMIHIGH/DIOLOW)" were all independently related to the worsening, and the PAF values (95 % CI) for worsening due to iBMIHIGH, iDIOLOW, and BMIHIGH/DIOLOW were 12.9 (3.2-18.4) %, 10.9 (5.0-13.9) %, and 31.4 (22.7-36.3) %, respectively. As much as 55 % of the worsening of glucose metabolism in the NGT subjects was attributable to increased BMI and/or attenuated BCF. The optimal cutoff for BMI was as low as 23.1 kg/m(2) in this population. We believe that these data should form the basis of future public health strategies for the prevention of diabetes in Japan.

Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes. Serum B12 concentrations, homocysteine plasma levels, the presence of retinopathy and history of macroangiopathy (stroke or coronary heart disease) were analyzed in patients without renal dysfunction (serum creatinine

To develop diabetes risk score (RS) based on the current definition of diabetes, we retrospectively analyzed consecutive 4,159 health examinees who were non-diabetic at baseline. Diabetes, diagnosed by fasting plasma glucose (FPG) ≥7.0 mmol/L, 2hPG ≥11.1 mmol/L and/or HbA1c ≥6.5% (48 mmol/mol), developed in 279 of them during the mean period of 4.9 years. A full RS (RSFull), a RS without 2hPG (RS-2hPG) and a non-invasive RS (RSNI) were created on the basis of multivariate Cox proportional model by weighted grading based on hazard ratio in half the persons assigned. The RSs were verified in the remaining half of the participants. Positive family history (FH), male sex, smoking and higher age, systolic blood pressure (SBP), FPG, 2hPG and HbA1c were independent predictors for RSFull. For RS-2hPG, 7 independent predictors, exclusive of 2hPG and smoking but inclusive of elevated triglycerides (TG) comparing to RSFull, were selected. FH, male sex, and higher age, SBP and HbA1c were independent predictors in RSNI. In the validation cohort, C-statistic (95%CI) of RSFull, RS-2hPG and RSNI were 0.80 (0.76-0.84), 0.75 (0.70-0.78) and 0.68 (0.63-0.72), respectively, which were significantly different from each other (P

Anjana et al. (1) analyzed the rate of worsening of glucose metabolism in subjects with normal glucose tolerance (NGT) and impaired fasting glucose (IFG)/impaired glucose tolerance (IGT), the rate of regression from abnormal glucose metabolism to NGT, and the risk factors for the worsening in an Asian Indian cohort. The study may be a valuable addition to the previously accumulated knowledge in the epidemiology of the diabetes evolution. However, we are afraid that the classification of glucose tolerance categories and terminology were confusing and misleading in their study. Namely, the current definition of prediabetes by the American Diabetes Association is …

Risk profile for incident chronic kidney disease (CKD) in Japanese subjects has not been established. Our aim was to identify risk factors for CKD in Japanese.Consecutive 171 536 health examinees (median age 49 years and estimated glomerular filtration rate (eGFR) 78.2 mL/min per 1.73 mIn the Derivation cohort, CKD developed in 1002 (5.8%) subjects. Seven variables such as lower eGFR, male gender, higher uric acid concentration, lower red cell count and higher age and systolic blood pressure were identified as significant risks for CKD, with lowered eGFR being an overwhelmingly strong risk: adjusted hazard ratio for those with the baseline eGFR70 mL/min per 1.73 mSeven risk factors for incident CKD were identified in Japanese health examinees. However, lowered baseline eGFR outweighed other risks to the degree that eGFR alone was suffice for CKD prediction.

Objective We undertook an investigation on the frequency and magnitude of elevated serum immunoglobulin G (IgG), and effects of treatment with L-thyroxine (T4) in patients with Hashimoto's thyroiditis. Methods Ninety-seven consecutive cases of Hashimoto's thyroiditis, 104 patients with simple goiter, and 75 normal subjects were analyzed retrospectively. Serum total T4, thyroid stimulating hormone (TSH), microsomal hemagglutination antibody (MHA) titer, and IgG were determined in all subjects. Results IgG was significantly elevated in patients with Hashimoto's thyroiditis as a group, and elevation above the upper limit of the normal range was found mostly in patients with hypothyroidism. There is a significant negative correlation between serum total T4 and IgG, and a significant positive correlation between TSH and IgG in patients with Hashimoto's thyroiditis. In addition, MHA titer was positively correlated with serum IgG. In a longitudinal analysis of hypothyroid patients with Hashimoto's thyroiditis, restoration of euthyroidism by L-T4 administration was associated with a consistent decrease in serum IgG. Conclusion Serum IgG concentration is increased in patients with Hashimoto's thyroiditis, particularly in hypothyroid patients, and treatment with L-T4 in such patients lowers IgG levels.

Mortality, macroangiopathic events and end-stage renal disease (ESRD) in the elderly under long-term, intensive multifactorial diabetes control were prospectively investigated. Three hundred and eighty-eight elderly patients (> or =65 years) with type 2 diabetes (the mean age 72.9 years, men/women ratio 176/212) were followed-up for 6 years with HbA1c 7.0%, BP 145/80 mmHg and total cholesterol

An 87-year-old man was admitted with fatigue, anorexia, vomiting, urinary incontinence, and a depressive state. His consciousness was evaluated as a 13 on the Glasgow Coma Scale (E4V3M6), and he had a body temperature of 36.4°C, a blood pressure of 91/60 mmHg, and a heart rate of 88 beats/min. General laboratory data were unremarkable except for a mildly elevated serum creatinine level. The plasma levels of growth hormone, luteinizing hormone, and follicle stimulating hormone were depressed. On the other hand, the prolactin level was elevated, and the corticotropin, cortisol, and thyrotropin levels were within the reference ranges. Cranial magnetic resonance imaging (MRI) revealed the marked swelling of the pituitary gland and the infundibular stalk, and the serum immunoglobulin G4 (IgG4) level was elevated (2.85 g/L; reference range, 0.048-1.05 g/L). Accordingly, a diagnosis of IgG4-related autoimmune hypophysitis (AH) was made. The patient responded well to glucocorticoid therapy, but the presence of diabetes insipidus was revealed and was subsequently controlled using desamino-D-arginine vasopressin (DDAVP). To our surprise, an empty sella was apparent on an MRI examination performed on Day 12. The patient's serum IgG4 level had decreased in a log-linear manner with a half-life of 30 days, which was comparable to the half-life of IgG4 in control subjects (21 days). At a 16-month follow-up examination, no substantial changes in the morphology or function of the pituitary gland were noted. In conclusion, an empty sella developed within 12 days after the clinical onset of AH in the present case, suggesting that an empty sella may be the direct outcome of AH. The conversion of AH to an empty sella was associated with an immediate shutdown of IgG4 overproduction.

Because vascular endothelial cell growth factor (VEGF) and transforming growth factor-beta (TGF-beta) are both involved in cellular growth and differentiation, we examined whether VEGF modifies TGF-beta signaling cascade in human umbilical cord vein endothelial cells (HUVEC). Production of plasminogen activator inhibitor-1 (PAI-1), which is under the specific control of TGF-beta, was strongly enhanced (3.5-fold) by TGF-beta treatment. Remarkably, physiological concentration of VEGF (30 nm) profoundly (by 60%) attenuated the TGF-beta stimulation of PAI-1 production without an effect on the basal PAI-1 production. In HUVECs transiently transfected with an expression construct containing a PAI-1 promoter fused to luciferase reporter gene, TGF-beta-stimulation of transcription of PAI-1 was clearly (by 60%) inhibited by VEGF. TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action in the human endothelial cell, specifically at the level of transcription of PAI-1 gene and Smad2/3 phosphorylation.

To elucidate the hierarchy in the evolution of glucose intolerance in the general population, the relationship between plasma glucose (PG), beta-cell function (insulinogenic index [II] = DeltaIRI(0-30)/DeltaPG(0-30) on 75 g oral glucose tolerance test [OGTT], where IRI is immunoreactive insulin), insulin sensitivity (Si; determined by quantitative insulin sensitivity check index [QUICKI]), age, and body mass index (BMI) were analyzed in 504 Japanese health examinees (men/women: 347/157). The mean (+/-SD) age was 53 (+/-11) years, BMI 23.6 (+/-3.2) kg/m2, fasting PG (FPG) 5.61 (+/-0.97) mmol/L, 2-hour PG 7.42 (+/-3.1) mmol/L, II 74.2 (+/-169.3) [pmol/L]. [mmol/l](-1), and QUICKI 0.385 (+/-0.057) [log (microU/mL) + log (mg/100 mL)](-1). Higher FPG and 2-hour PG, respectively, were independently correlated with lower II, lower QUICKI, higher age, and higher BMI; the standardized correlation coefficient was largest for the correlation between PG and II. Based on the multiple linear regression, FPG = 8.565 - 1.201. log [II] - 5.374. QUICKI + 0.007. age + 0.030. BMI (r2 = 0.442), and 2-hour PG = 14.239 - 4.206. log [II] - 0.141. QUICKI + 0.034 - age + 0.141. BMI (r2 = 0.493). Thus, elevation of PG correlated most prominently with beta-cell dysfunction and less prominently with decreased Si, higher age, and BMI (especially so in the case of 2-hour PG). In conclusion, the primacy of beta-cell dysfunction in the process of developing glucose intolerance was strongly suggested in the Japanese general population.

Although "polar triiodothyronine (T(3)) syndrome" in chronic dwellers/workers in Antarctica has been established, alteration of the pituitary thyroid-axis upon accidental hypothermia is not well recognized. We report here a rare case of elevation of thyrotropin (TSH) upon accidental hypothermia.A 75-year-old man was admitted because of consciousness disturbance.The mean outside temperature was approximately -2.0°C (28.4°F) but his house was inadequately heated. His rectal temperature was 29.5°C (85.1°F). Goiter was not palpable and pitting edema, not myxedema, was present. Serum TSH was elevated (28.3 mU/L, reference range 0.27-4.2), and free T(3) (FT(3)) and free thyroxine (FT(4)) lowered (FT(3), 3.25 pmol/L with a reference range of 4.00-7.85, and FT(4), 9.18 pmol/L with a reference range of 12.87-23.179), but thyroid-related autoantibodies were all negative. By the next morning, body temperature had risen to36°C (96.8°F) and there was no further recurrence of hypothermia. Serum TSH decreased exponentially and the patient's condition had become normal by day 22. FT(3) and FT(4) were found to be slightly lowered and elevated, respectively, during the same period, in the subnormal range. At the end of the observation period, the patient settled into the state known as "nonthyroidal illness syndrome."Elevation of TSH in an elderly patient with accidental hypothermia was normalized after restoration of normal body temperature. Elevation of TSH upon accidental hypothermia was probably an adaptive response.In patients with accidental hypothermia, the possibility of an adaptive elevation of TSH should be borne in mind. This clearly warrants further studies of the adaptation of the pituitary-thyroid axis in patients with accidental hypothermia.

Whole pancreas or β-cell transplantation has opened the way for the treatment of advanced stage of diabetes mellitus. However, it is always limited by the scarcity of transplantation materials. The amniotic membrane is part of the fetal membrane and is composed of amniotic epithelium (HAE) and mesenchymal (HAM) cells that are derived from the inner cell mass in the blastocyst. Thus, HAE and HAM cells may have the potential to differentiate into various organs. The aim of our study was to assess the possibility of HAE cells differentiating into insulin-producing cells. In vitro, HAE cells stimulated with nicotinamide induced insulin mRNA in the culture cells. In vivo, HAE cells were capable of normalizing the blood glucose level of diabetic mice after several weeks of implantation into streptozotocin-induced diabetic mice. The distribution of human cells and human insulin secretion in mouse tissue studied by immunohistochemistry for anti-human-specific β-2-microglobulin and anti-human-specific insulin shows the same location in mouse tissue. These studies suggest that HAE cells have the potential to differentiate into β-cells in vivo, and hence that HAE cells have therapeutic potential for the treatment of type I diabetes mellitus.

We appreciate the comments by Dr Kawada [1] on our recent article [2] that confirmed 1-h plasma glucose value on an oral glucose tolerance test as a better predictor of the development of Type 2 diabetes than fasting or 2-h plasma glucose values. His letter contained three comments regarding our article that we address here. This article is protected by copyright. All rights reserved.

Effects of growth hormone (GH), insulin-like growth factor I (IGF-I), and endothelin-1 (ET-1) on endothelial cell migration and the underlying molecular mechanisms were explored using a human umbilical cord endothelial cell line, ECV304 cells, in vitro. Treatment of the cells with IGF-I or ET-1, but not GH, stimulated the cell migration. Interestingly, however, ET-1-induced, but not IGF-I-induced, migration of the cells was inhibited by GH. Both ET-1 and IGF-I caused activation of mitogen-activated protein kinase (MAPK) in the cells, and GH eliminated the MAPK activation produced by ET-1 but not that produced by IGF-I. On the other hand, migration of the cells was stimulated by protein kinase C (PKC) agonist, phorbol 12-myristate 13-acetate. ET-1 promoted PKC activity, and a PKC inhibitor, GF-109203X, blocked ET-1-induced cell migration. Although GH inhibited ET-1-induced cell migration and MAPK activity, it did not block ET-1-induced PKC activation. Thus ET-1 stimulation of endothelial cell migration appears to be mediated by PKC/MAPK pathway, and GH may inhibit the MAPK activation by ET-1 at the downstream of PKC.

Background: There are few reports on long-term convalescence with regard to cardiac injury caused by blunt chest trauma. Nuclear medicine study of the heart (NMSH) in the early stages of injury is reportedly superior to detect the correlation between injury and fatal arrhythmia. Therefore, we prospectively performed NMSH and Holter electrocardiogram (ECG) in the early and chronic stages for a cardiac injury patient, and we longitudinally examined the recovery process and the occurrence of fatal arrhythmia. Methods and Results: A total of 202 patients with blunt chest trauma were admitted to our hospital between April 2006 and January 2007. Of 65 patients who were diagnosed with cardiac injury by ECG, a myocardial enzyme, or cardiac ultrasonography, 11 were enrolled in this study because they agreed to outpatient visiting for regular examinations for 1 year. NMSH showed positive findings in 6 of the 11 patients in the acute period of < 1 month. Twelve months later, five patients improved but still exhibited protracted cardiac damage without complete recovery. Among the six patients in whom NMSH showed positive findings, Holter ECG indicated an abnormal finding in two patients in the acute period and in four patients in the chronic period, and detected one patient with a nonsustained ventricular tachycardia in the chronic period. Conclusion: Cardiac injuries may exacerbate cardiac functions and lead to fatal arrhythmia during the chronic period. Therefore, evaluating recovery for at least 12 months after myocardial damage is necessary to prevent sudden cardiac death.

Recent studies revealed favorable para- and/or autocrine effects of IGF-1 in the pathogenesis of diabetic complications. On the other hand, hyperglycemia is a risk factor for the development of diabetic vascular complications. In this study we examined the effects of high glucose and/or IGF-1 on cell migration and angiogenesis (tubular formation) by using human endothelial cells (EC) in vitro. First we examined cell migration by the two-chamber method. Chronic treatment with a high concentration of D-glucose strongly stimulated the cell migration, which was mimicked by PMA, a protein kinase C (PKC) agonist. The cell migration was also induced by IGF-1. The glucose-induced cell migration was blocked by PKC inhibitor, H7. IGF-1-induced cell migration was not blocked by PD98059, MAPK/ERK kinase (MEK) inhibitor or wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor. Next we examined the effects of high glucose and/or IGF-1 on the tubular formation of EC. The tubular formation was induced only when the cells were exposed to a combination of high glucose and IGF-1. The tubular formation was blocked by MEK inhibitor and PI 3-kinase inhibitor but not by PKC inhibitor. These results indicate that hyperglycemia and IGF-1, respectively, stimulate the EC migration, and tubular formation is induced by a combination of IGF-1 and hyperglycemia.

Graves' disease is an autoimmune disorder characterized by the presence of antibodies against thyrotropin receptor (TRAb). Stem cell factor (SCF), derived from bone marrow, is known to promote lymphohematopoiesis. To investigate the relation between the alteration in plasma levels of SCF, thyroid hormone status, and TRAb measured by thyrotropin binding inhibition (TBI), 13 untreated, 21 treated, and 4 relapsed hyperthyroid Graves' disease patients, 21 patients with Hashimoto's thyroiditis, 6 patients with subacute thyroiditis, and 11 control subjects were examined. In untreated hyperthyroid Graves' disease patients, serum levels of thyroxine (T4) and triiodothyronine decreased rapidly by methimazole treatment, and TBI decreased progressively, but variably. Simultaneously, the elevated plasma levels of SCF decreased gradually and progressively. The plasma levels of SCF correlated curvilinearly with the serum levels of T4. In 4 patients with relapsed hyperthyroid Graves' disease, TBI was marginally positive in 3 patients and negative in 1, but plasma levels of SCF were elevated significantly in all 4 patients. In patients with subacute thyroiditis and Hashimoto's thyroiditis with or without T4 replacement, plasma levels of SCF did not differ from that of controls. These findings indicate that the elevation of plasma levels of SCF relates to the longstanding thyrotoxic state and that short-term thyrotoxicosis does not significantly affect plasma levels of SCF. It remains to be determined whether the elevation in plasma levels of SCF is induced by excess thyroid hormone, reflecting the hypermetabolic state, or whether the elevation of plasma levels of SCF contributes to stimulation of lymphocytes producing TRAb.

Analysis of patients with persistent hypothyroidism due to Hashimoto's thyroiditis suggested that metabolism of thyroxine (T4), including deiodination to triiodothyronine (T3), was reduced in the elderly. The increase in the serum levels of T4 after oral administration of T4 was augmented in the elderly, whereas increase in the serum T3 level was not. Possibly due to the reduction in the pituitary deiodinase, suppression by T4 administration of serum thyrotropin (TSH) level was the same in elderly as in younger subjects despite a larger increase in the serum levels of T4 in the elderly. Consequently, the amount of T4 required to maintain a normal serum TSH level did not differ between elderly and younger subjects. Other characteristics of elderly patients with Hashimoto's thyroiditis were that goiter size was smaller, that hypothyroidism was more frequent, and that Graves' disease was less frequent.

The role of the renin-aldosterone system and the ability of renal sodium reabsorption to facilitate pressure natriuresis were analyzed by using a sufficient number of Japanese patients with essential hypertension.We studied 3222 normal Japanese subjects (610 in Kashiwa City Hospital and 2612 in Shinshu University Hospital), 741 Japanese patients with essential hypertension (256 in Kashiwa City Hospital and 485 in Shinshu University Hospital), 20 patients with aldosterone-producing adenomas and 11 patients with idiopathic hyperaldosteronism to determine the possible roles of sodium, renal function, and plasma aldosterone concentration (PAC) on blood pressure elevation. Inappropriate elevation of aldosterone levels [elevation of the aldosterone:plasma renin activity (PRA) ratio] was used to assess aldosterone action.The peak of the serum sodium distribution curve was approximately 2 mmol/l higher in the patients with essential hypertension than it was in controls. The prevalence of higher serum sodium concentrations (or = 147 mmol/l) also was increased significantly hypertensive patients. Age-related deterioration of renal function did not explain the hypertension and abnormal sodium metabolism in the hypertensive patients. In stepwise regression analysis, the serum sodium concentration was related inversely to the PRA and positively to the PAC:PRA ratio. Although there was an inverse relationship between urinary sodium excretion (representing sodium intake) and the PRA, urinary sodium excretion proved not to be significant as a source of variation in the PAC or in the PAC:PRA ratio in the hypertensive patients. Although the PAC was within the normal range in patients with serum sodium concentrations of 147 mmol/l or more and an elevated PAC:PRA ratio, it was inappropriately high for the stimulus applied, as indicated by the PRA; this is similar to the situation with aldosterone-producing adenomas or idiopathic hyperaldosteronism.Serum sodium distribution patterns differed between normal subjects and patients with essential hypertension in this Japanese population. The deterioration of renal function and increased sodium intake did not explain this abnormal sodium metabolism. A higher serum sodium concentration is related to an elevated blood pressure, and, in some patients, an inappropriate elevation of plasma aldosterone levels. Of the Japanese hypertensive patients, 10-14% exhibited serum sodium concentrations of 147 mmol/l or more and inappropriate elevations of aldosterone level (suppressed PRA and normal aldosterone level). The defect in these patients presumably lies in the inappropriately high secretion of aldosterone.

The risk factors for impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have yet to be established. Our aim was to elucidate the predisposing factors for IFG and IGT in Japanese subjects with normal glucose tolerance (NGT). Using a 75 g oral glucose tolerance test (OGTT), we analyzed 604 adults with the ADA-defined NGT. Follow-up glucose tolerance status was determined by 75 g OGTT performed 3.7 yrs later. Glucose-stimulated insulin secretion (GSIS), whole body insulin sensitivity (SI) and beta cell function (BCF) were estimated by Stumvoll indices, ISI(Matsuda), and a product of Stumvoll 1(st) and ISI(Matsuda), respectively, and hepatic SI by quantitative insulin sensitivity check index. Logistic regression analysis revealed that attenuated BCF due to low GSIS was an independent risk factor for IFG. Low whole body SI was an additional risk for IGT. Male gender and high BMI were independently related to the progression to both IFG and IGT, whereas a positive diabetes family history was independently related to IGT. The worsening of glucose tolerance at large was predicted with 66% sensitivity by risk engine with GSIS, whole body SI, gender, BMI and glucose. This finding may help when implementing early intervention strategies for diabetes.

To evaluate the switching from an angiotensin receptor blocker (ARB) to a drug combination containing an ARB and a diuretic drug in terms of effects on hypertension, cardiac load, and cardiac function.In a study conducted on 82 patients with a history of heart failure and hypertension who had been treated with an ARB but failed to reach the target blood pressure, ongoing oral ARB treatment was switched to a drug combination of losartan and hydrochlorothiazide (HCTZ). Using ambulatory blood pressure monitoring (ABPM), the variations in blood pressure and the effects on cardiac load and cardiac function were evaluated before and after treatment.Comparison of the ABPM findings before and after switching treatment showed significant improvements in mean systolic and diastolic blood pressure, improvements in systolic and diastolic blood pressure 1 hour before getting out of bed, and improvements in the plasma levels of human brain natriuretic peptide as an indicator of cardiac load.The drug combination of losartan and hydrochlorothiazide showed a stronger antihypertensive effect than that of the conventional ARB and improved heart function.

Aims To investigate whether the elevation of liver enzymes is associated with the progression from normal to impaired glucose tolerance. Methods A historical cohort study was conducted in 594 male workers at public schools, who had normal glucose tolerance at baseline. The progression to impaired glucose tolerance and impaired fasting glycaemia during a mean follow-up of 3.1 years was measured using an oral glucose tolerance test. Results Overall, 141 (23.7%) subjects developed impaired glucose tolerance and 68 (11.4%) subjects developed impaired fasting glycaemia, 23 of whom had combined impaired fasting glycaemia/impaired glucose tolerance. The incidence of impaired glucose tolerance increased significantly with increasing quartiles of serum aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase (P for trend

1. This study examines whether the supplementation of isoflavones (ISO) exerts beneficial effects on the bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DEXA). 2. Eighty-one healthy Japanese pre- and postmenopausal women were randomly assigned to the following two groups taking either ISO (100 mg) tablets (ISO group) or placebo tablets (P group) containing vitamins C (25 mg) and E (5 mg) daily for 24 weeks in a double-blind placebo controlled parallel design. 3. Seventy women completed the intervention study (34 on ISO, 36 on P), only ISO group was proven to increase significantly BMD (P < 0.05 vs before) and to significantly decrease body fat measured by the DEXA (P < 0.0001 vs before and P < 0.05 vs P group), while BMI was maintained in ISO group despite significant BMI increase in P group. Thus, percent changes in BMI were significantly different between ISO and P groups (P < 0.05) 24 weeks after the intervention. 4. This prospective DEXA study confirmed a long-term ISO supplementation, 100 mg/day could not only prevent menopausal bone resorption but also increase BMD and decrease body fat concomitantly with BMI reduction. Enough ISO supplementation may contribute to the risk reduction of osteoporosis and obesity and, thus to overall health promotion in menopausal women.

In fulminant type 1 diabetes (FT1D), irreversible destruction of pancreatic beta-cells occurs abruptly, leading to sudden diabetic ketoacidosis (DKA) in the absence of diabetes-related autoantibodies. This is the first case report of FT1D in which beta-cell was rescued with the commencement of insulin therapy during the evolution of FT1D.

Aim To identify predictors of coronary heart disease (CHD) in Japanese patients with type 2 diabetes (T2DM). Methods A matched case-control study was performed using 800 patients with T2DM admitted for treatment of hyperglycemia from January 2002 to June 2010. Cases comprised 16 patients who had developed acute myocardial infarction and/or received a coronary artery bypass by June 2010, and controls comprised 48 age- and sex-matched patients without CHD events. The mean age, glycated hemoglobin (HbA1c), and body mass index (BMI) were 61.5 yrs, 9.7% and 24.4 kg/m(2), respectively. The relationship of baseline variables, including lipid values, HbA1c, BMI, blood pressure, fasting blood sugar, 2h-post-breakfast blood sugar, delta blood sugar(0-2h), urinary albumin excretion, estimated glomerular filtration rate and treatment modalities (insulin/sulfonylurea/biguanide), to CHD development was analyzed by conditional logistic regression analysis. Results Total cholesterol (TC) (OR 2.35, 95%CI 1.11-4.98, p=0.03), non-HDL-cholesterol (OR 3.07, 95%CI 1.33-7.10, p=0.009), LDL-cholesterol (OR 2.84, 95%CI 1.24-6.51, p=0.01), non-HDL-cholesterol/HDL-cholesterol (OR 2.07, 95%CI 1.10-3.90, p=0.02) and LDL-cholesterol/ HDL-cholesterol (OR 2.74, 95%CI 1.22-6.15, p=0.01) were significantly related to CHD. Fold risk increment per 1-SD increase in basal TC, non-HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol was 2.33, 2.89, 2.52, 2.37 and 2.60, respectively. Only non-HDL-cholesterol was an independent risk factor. From the receiver operating characteristic curve, 3.89 mmol/L non-HDL-C was the best cutoff value. None of the non-lipid variables were significantly related to CHD. Conclusion Non-HDL-cholesterol was the most dominant predictor of the development of CHD in Japanese patients with T2DM.

Aim of this study was to formulate an index for glucose effectiveness (Sg), SgIo, based on 3-point (0, 30 and 120 min) 75 g oral glucose tolerance test (OGTT). The equation for SgIO was developed in the Chikuma cohort (n = 502). Firstly, post-loading plasma glucose without insulin action and Sg (PPG-without insulin and Sg) was calculated as follows: fasting plasma glucose (mg/dl) + [0.75 × 75,000]/[0.19 × BW(kg) × 10]. Secondly, ‘PPG-without insulin/with Sg’ was obtained from inverse correlation between log10DIO and 2-h post-glucose plasma glucose at OGTT (2hPG) in each glucose tolerance category: DIO denotes oral disposition index, a product of the Matsuda Index and δIRI0–30/δPG0–30. Thirdly, expected 2hPG (2hPGE) of a given subject was obtained from the regression, and the ratio of 2hPG to 2hPGE (2hPG/2hPGE) was determined as an adjustment factor. Lastly, SgIO ([mg/dl]/min) was calculated as \( \frac{{[{\text{PPG}} \hbox{-} {\text{without}}\;{\text{insulin}}\;{\text{and}}\;{\text{Sg}}] - [{\text{PPG}} \hbox{-} {\text{without}}\;{\text{insulin}}/{\text{with}}\;{\text{Sg}}] \times [(2{\text{hPG}})/(2{\text{hPG}}_{\text{E}})]}}{120} \). SgIO was validated against Sg obtained by frequently sampled intravenous glucose tolerance test in the Jichi cohort (n = 205). Also, the accuracy of prediction of Sg by SgIo was tested by the Bland–Altman plot. SgIO was 3.61 ± 0.73, 3.17 ± 0.74 and 2.15 ± 0.60 in subjects with normal glucose tolerance (NGT), non-diabetic hyperglycemia and diabetes, respectively, in the Chikuma cohort. In the Jichi cohort, SgIO was significantly correlated with Sg in the entire group (r = 0.322, P < 0.001) and in subjects with NGT (r = 0.286, P < 0.001), and SgIo accurately predicted Sg. In conclusion, SgIO could be a simple, quantitative index for Sg.

A 78-yr-old man was admitted in emergency with fatigue, anorexia, vomiting, hypothermia (35.1 °C on a hot August day), hypotension (89/56 mmHg) and hyponatraemia (126 mEq/l). Plasma corticotropin and cortisol were severely depressed: 0.84 pmol/L and 33.1 nmol/L respectively (reference range, 1.5-13.9 pmol/L and 110-505 nmol/L, respectively). Thyroid stimulating hormone was low-normal and free-triiodothyronine and free-thyroxine were subnormal. Magnetic resonance imaging revealed swelling of the pituitary gland and the stalk. The patient recovered after glucocorticoid replacement (200 mg/day intravenous hydrocortisone on Day 1 followed by tapering). Central diabetes insipidus which had become apparent had been treated with 1-desamino-8-D-arginine vasopressin. A surge of corticotropin and cortisol, 19.4 pmol/L and 712.1 nmol/L respectively, was found on Day 5 when luteinizing hormone, follicle stimulating hormone, and testosterone were subnormal and prolactin was slightly elevated. Subsequently, corticotropin and cortisol levels normalized together with normalization of luteinizing hormone, follicle stimulating hormone, anti-diuretic hormone, thyroid stimulating hormone, prolactin, testosterone and thyroid hormone levels. Shrinkage of the pituitary gland occurred after one month. Serum immunoglobulin G4 was elevated (3.21 and 6.02 g/l at 1- and 3-month follow-ups respectively). In conclusion, a paradoxical surge of corticotropin after glucocorticoid replacement was observed in a patient with central adrenal insufficiency due to immunoglobulin G4-related hypophysitis. Surge of ACTH in central adrenal insufficiency after glucocorticoid replacement has rarely been reported, and this is the second such case report.

Objective: To determine whether there is an age-related difference in the therapeutic response to antithyroid drugs in hyperthyroid Graves' disease. Design: Retrospective analysis of treatment duration and recurrence rate. Patients: Two hundred and twenty-two patients who have triiodothyronine-suppressible thyroids within 4 years of methimazole treatment. Measurements: Serum thyroid hormone levels, serum thyrotropin receptor antibody titer, and thyroidal radioiodine uptake. Main results: A longer period of methimazole treatment was needed to normalize serum thyroid hormone levels and to restore normal thyroidal triiodothyronine suppressibility in young than in aged patients. There was an average 10-month lag between normalization of thyrotropin receptor antibody titer and restoration of thyroidal triiodothyronine suppressibility in both young and aged patients. Recurrence after discontinuation of methimazole was more frequent in young than in aged patients. Conclusions: Aged patients with hyperthyroid Graves' disease show a more favorable response to antithyroid drugs than young counterparts.

Glucose induces biphasic insulin secretion by the islet beta-cell. Based on recent knowledge on glucose signaling in the beta-cell, the underlying mechanisms for this biphasicity could be envisaged as follows. Glucose-induced elevation of cytosolic free Ca(2+) concentration, which is due to the electrophysiological events that originate in closure of the ATP-sensitive K(+) (K(ATP)) channel, most likely triggers the first phase. The second phase is produced by gradual augmentation and potentiation of Ca(2+)-triggered insulin release by the K(ATP) channel-independent, nonionic signals. Protein acylation may be involved in the nonionic signaling. In patients lacking functional K(ATP) channels, however, the first phase of glucose-induced insulin secretion is clearly retained, casting doubt on the simplistic view outlined above. In this pathological condition, the K(ATP) channel-independent, most likely nonionic, glucose action alone is sufficient for the first-phase response.

We present the case of a 65-year-old man with a pancreatic nonfunctioning neuroendocrine tumor causing main pancreatic duct obstruction that presented as excessive hyperglycemia. We considered the tumor elicited worsening of diabetes in this case, and we performed review of the relevant literature.

The relationship between insulin sensitivity (Si) and insulin secretion (β) was analyzed in 533 health examinees. The subjects underwent a 75 g oral glucose tolerance test, with plasma glucose (PG) and immunoreactive insulin (IRI) determined at fasting, 30 min and 120 min, and were classified according to the current criteria as normal glucose tolerance (NGT, n=328), non-diabetic hyperglycemia (NDH, n=113) including impaired fasting glucose and impaired glucose tolerance, and diabetes mellitus (DM, n=72). NGT was subdivided by fasting PG (FPG) tertile, ≤4.9, 5.0-5.4 and 5.5-6.0 mM, into NGT(FPG1), NGT(FPG2) and NGT(FPG3), or by body mass index (BMI) tertile, ≤21.8, 21.9-24.4 and ≥24.5 kg/m², into NGT(BMI1), NGT(BMI2) and NGT(BMI3). As an index of Si and β, Matsuda index=10,000/sqrt[FPG·FIRI·2hPG·2hIRI] and δIRI₀₋₃₀/δPG₀₋₃₀, were employed respectively: FIRI, 2hPG and 2hIRI denote fasting IRI, 2h-post glucose PG and IRI, respectively. Correlation between Si and β was evaluated by Spearman's rank correlation and the parameters for [β]=a·[Si](b) were obtained by standardized major axis (SMA) regression. Si-β correlation was strongest in NDH (Spearman's rho=-0.546, SMA regression r²=0.277), intermediate in DM (rho=-0.432, r²=0.193) and weakest in NGT (rho=-0.201, r²=0.039). Spearman's rho for the Si-β correlation was significantly lower in NGT than in NDH (p=0.003). Si-β correlation was significant in NGT(FPG3), NGT(FPG2) and NGT(BMI3), but not in NGT(FPG1), NGT(BMI2) and NGT(BMI1). The slope, b, was -1.184˜-1.530 without significant differences between any groups. In conclusion, the hyperbolic Si-β correlation was weaker in NGT than in NDH and absent in NGT subjects belonging to the lowest FPG or BMI tertile.

A 29-year-old female patient presented with shock and dyspnea due to heart failure and pulmonary edema. Echocardiography indicated excessive contraction limited to the left ventricular apex and akinesis of the basal and middle ventricle, which were confirmed by emergency left ventriculography. The finding was diagnostic of inverted Takotsubo cardiomyopathy. An abdominal computed tomography scan showed a tumor in the left adrenal gland with a central low-density area, and the plasma and urinary catecholamines were strikingly elevated. Taken together, these findings suggested the presence of a hemorrhagic pheochromocytoma. A myocardial biopsy in the very acute stage on the day of admission revealed neutrophilic infiltration and contraction-band necrosis, which was indistinguishable from the previously reported pathology in the acute phase of idiopathic Takotsubo cardiomyopathy without pheochromocytoma. The diagnosis of pheochromocytoma in this case was confirmed 7 weeks later by surgical removal of the left adrenal gland with massive hemorrhage at the center of the pheochromocytoma. The marked similarity of the endomyocardial pathology between this case and cases with idiopathic Takotsubo cardiomyopathy strongly points to catecholamine excess as a common causality for Takotsubo cardiomyopathy with or without pheochromocytoma.