Vulnerable Hours of the Day for Severe Iatrogenic Hypoglycaemia in Type 2 Diabetes: A Single-Centre Retrospective Study.

INTRODUCTION: Iatrogenic hypoglycaemia is an event that should be avoided in the treatment of diabetes, but the pathophysiology thereof has been poorly examined and reported. There is no established method for preventing iatrogenic hypoglycaemia and the current approach is a reactive response following onset of the disease. In this study, we aimed to explore the existence of 'hypoglycaemia-vulnerable hours of the day' in patients with type 2 diabetes, with the ultimate goal of preventing the onset of iatrogenic hypoglycaemia by clarifying the time when severe hypoglycaemia is likely to occur. METHODS: Of the 553,201 patients who visited the Critical Care and Emergency Center of Aizawa Hospital between 2008 and 2019, patients with proven hypoglycaemia (blood glucose level <3.0 mmol/L) and those using insulin or oral hypoglycaemic agents for the treatment of type 2 diabetes were included: 146 insulin users and 148 oral hypoglycaemic agent users. Cosinor analysis was employed to identify hypoglycaemia-vulnerable hours of the day. RESULTS: Patients with type 2 diabetes and severe hypoglycaemia had two peaks: at 8:00 and 18:00-19:00. Hypoglycaemia was observed as quadra-peaked in insulin users and double-peaked in oral hypoglycaemic agent users. Single-cosinor analysis revealed that the cycle was 5.83 hours (R=0.417) in insulin users, whereas it was 11.0 hours (R=0.717) in oral hypoglycaemic agent users. In insulin users, a significant periodicity of six hours (P=0.003) was observed in the cosinor detection analysis, and a significant correlation (P<0.05) was present in the cosinor percent rhythmicity analysis. In contrast, in oral hypoglycaemic agent users, a significant periodicity of 11 hours (P=0.03) was ascertained in the cosinor detection analysis, and there was a significant correlation (P<0.001) in the cosinor percent rhythmicity analysis. There were different hypoglycaemia-vulnerable hours of the day in the patients with type 2 diabetes, suggesting an interaction between disease pathophysiology and pharmacology. CONCLUSIONS: These results can help elucidate the trend of the development of iatrogenic hypoglycaemia and contribute to the prevention of the onset thereof.

Hemoglobin Glycation Index: A Novel Risk Factor for Incident Chronic Kidney Disease in an Apparently Healthy Population.

CONTEXT: Chronic kidney disease (CKD) is a worldwide health problem. Recent literature has shown an association of hemoglobin glycation index (HGI) and CKD in patients with dysglycemia. OBJECTIVE: The aim of this study was to reveal the impact of HGI as a predictor for incident CKD in the general population. METHODS: CKD was defined as dipstick proteinuria or estimated glomerular rate (eGFR) < 60 mL/min/1.73 m2. Impact of HGI on incident CKD was assessed using the data from CKD-free health examinees (N = 23 467, 4.1% with diabetes) followed for a mean of 5.1 years: Cox proportional hazards model was employed with multivariate adjustment for age, systolic blood pressure, eGFR, fasting plasma glucose, body mass index, log[alanine aminotransferase], log[triglycerides], high-density lipoprotein cholesterol, platelet counts, smoking, and sex. Elevated level of HGI in subjects with CKD was ascertained after propensity score matching of another group of health examinees (N = 2580, 7.6% with diabetes). RESULTS: In the former group, CKD developed in 2540 subjects and HGI was the second most robust predictor for CKD, following low eGFR. With adjustment for the 11 covariates, the hazard ratio of HGI (95% CI) for CKD was 1.293 (1.238 to 1.349) (P < .0001). The population attributable risk of HGI for CKD was 4.2%. In the latter group, among 708 subjects matched 1:1 for 9 covariates, HGI was significantly elevated in subjects with CKD (median [interquartile range] -0.208 [-0.504 to -0.156] vs -0.284 [-0.582 to 0.052], P = .03). CONCLUSION: HGI was a novel risk factor for CKD in the general population.

Dysglycemia With Impaired Insulin Secretion After Resection of a High-Molecular-Weight IGF-II-Producing Tumor.

Analysis of insulin and related glucoregulatory hormone secretion following high-molecular-weight insulin-like growth factor II (HMW-IGF-II)-releasing tumor excision has never been reported. In a man with chronic hypoglycemia-plasma glucose (PG), 2.1 mmol/L with undetectable serum insulin, less than 7.2 pmol/L on admission-the cause of the hypoglycemia was HMW-IGF-II in the serum secreted by an intrathoracic benign pleural solitary fibrous tumor (size: 15 × 17 × 12 cm). Removal of the tumor nullified serum HMW-IGF-II and hypoglycemia. Postoperative glucose metabolism was evaluated day 272 by 75 g oral glucose tolerance test (OGTT) and on days 5, 202, and 990 by fasted sampling. Glycated hemoglobin A1c (HbA1c) was 37 to 41 mmol/mol, fasting PG was 5.3 to 5.4 mmol/L, and 2-hour PG at 75 g OGTT was 6.9 mmol/L, indicating that he was at the prediabetes stage. Homeostasis Model Assessment 2 of Insulin Resistance and Homeostasis Model Assessment 2 of ß-Cell levels were within the normal range but the Stumvoll first phase was lowered. Insulin sensitivity and secretion were compared to age-, sex-, and body mass index-matched controls with normal glucose metabolism. Long-term HMW-IGF-II exposure of pancreatic islet ß cells caused the functional impairment, that is, suppressed glucose-stimulated insulin secretion (GSIS), leading to nondiabetic hyperglycemia. This fact suggests long-term HMW-IGF-II exposure of the islet ß cell specifically dampens GSIS.

Hepatic Steatosis and High-Normal Fasting Glucose as Risk Factors for Incident Prediabetes.

Context: The role of hepatic steatosis (HS) in the initial stages of developing type 2 diabetes remains unclear. Objective: We aimed to clarify the impact of HS indexed by Fatty Liver Index (FLI) and high-normal fasting plasma glucose (FPG) as risk factors for incident prediabetes in a nonobese cohort. Methods: Data from 1125 participants with ADA-defined normal glucose metabolism (median age 52 years; BMI 23.1 kg/m2) were used for retrospective analysis. In the entire population, correlation between normal FPG and FLI was evaluated by multiple regression adjusted for age and sex. Follow-up data from 599 participants in whom 75-g OGTT was repeated 3.7 years later showed that 169 developed prediabetes. This was analyzed by the multivariate Cox proportional hazards model. Results: In the entire population, FLI was positively correlated with FPG (P < 0.01): mean FLI increased from 15.8 at FPG 4.2 mmol/L to 31.6 at FPG 5.5 mmol/L. Analysis of the 599 participants (2061 person-years) by Cox model, adjusted for sex, age, family history of diabetes, ISIMATSUDA, and Stumvoll-1, clarified an increased risk of prediabetes with high-normal FPG and FLI. Risk was increased 2.2 times with FLI ≥ 16.5 vs FLI < 16.5, P < 0.001, and increased 2.1 times in participants with FPG ≥ 5.3 mmol/L, P < 0.001. Cutoff values (unadjusted) were obtained by ROC at the point of the largest Youden's index using the entire range of the variables. Conclusion: Even among nonobese individuals, HS indexed by FLI and a high-normal FPG (≥ 5.3 mmol/L) are risk factors for prediabetes, independently from insulin.

Reduction of Severe Hypoglycemic Events Among Outpatients with Type 2 Diabetes Following Sodium-Glucose Cotransporter 2 Inhibitor Marketing in Japan.

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<59.4 mg/dl (3.3 mmol/l) on the one hand and analyzed the prescription trend of hypoglycemic agents all over Japan on the other. Analysis of the annual number of hypoglycemic patients visited ER was performed at Aizawa Hospital, a medical center located in the midst of a city. The study duration was over 10 years from 2008 to 2019. We found a clear-cut decreasing trend of hypoglycemia over the 10 years, ca. 61/year to 39/year. Immediately after the release of sodium-glucose co-transporter-2 inhibitors, since 2013 to 2017, the decrease was rather sharp as 81/year to 31/year, and the change of the national number of its prescription inversely correlated with the change of the number of the patients with hypoglycemia. This was not the case immediately after the introduction of dipeptidyl peptidase-4 inhibitors in the Japanese market since 2008 to 2012. There was no significant correlation between its prescription and the number of patients with hypoglycemia. The data strongly suggested that there was a causal relationship exclusively between the introduction of sodium-glucose cotransporter-2 inhibitor, and the reduction of hypoglycemic events among patients with type 2 diabetes.

Prediction model of Graves' disease in general clinical practice based on complete blood count and biochemistry profile.

Although untreated Graves' disease (GD) is associated with a higher risk of cardiac complications and mortality, there is no well-established way to predict the onset of thyrotoxicosis in clinical practice. The aim of this study was to identify important variables that will make it possible to predict GD and thyrotoxicosis (GD + painless thyroiditis (PT)) by using a machine-learning-based model based on complete blood count and standard biochemistry profile data. We identified 19,335 newly diagnosed GD patients, 3,267 PT patients, and 4,159 subjects without any thyroid disease. We built a GD prediction model based on information obtained from subjects regarding sex, age, a complete blood count, and a standard biochemistry profile. We built the model in the training set and evaluated the performance of the model in the test set by using the artificial intelligence software Prediction One. Our machine learning-based model showed high discriminative ability to predict GD in the test set (area under the curve [AUC] 0.99). The main contributing factors to predict GD included age and serum creatinine, total cholesterol, alkaline phosphatase, and total protein levels. We still found high discriminative ability even when we restricted the variables to these five most contributory factors in our prediction model (AUC 0.97) built by using artificial intelligence software showed high GD prediction ability based on information regarding only five factors.

Coronavirus Disease 2019 and the Thyroid - Progress and Perspectives.

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.

Development of glomerular hyperfiltration, a multiphasic phenomenon.

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.

Homonymous quadrantanopia associated with hyperosmolar hyperglycemic syndrome.

We encountered a 64-year-old man with hyperosmolar hyperglycemic syndrome, having a sudden-onset homonymous right inferior quadrantanopia. This is the first documentation of such a phenomenon in hyperosmolar hyperglycemic syndrome. We believe this is a variant of hemianopia in patients with hyperglycemic hyperosmolar syndrome.

Startling hyperglycaemia with transient beta cell stunning in a patient with type 2 diabetes.

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, ß-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 (<0.03 U/mL), C-peptide immunoreactivity (CPR) undetectable (<0.003 ng/mL), and anti-glutamic acid decarboxylase antibody negative. Following the above-described treatment, fasting PG was 186 mg/dL and CPR 1.94 ng/mL, respectively, on Day 14; 2-h post-breakfast PG 239 mg/dL and CPR 6.28 ng/mL, respectively, on Day 18. The patient discharged on Day 18 with 1,800 kcal diet, 32 U insulin glargine and 40 mg gliclazide. Fifteen months later at outpatient clinic, her HbA1c was 6.9% and 2-h post-breakfast PG 123 mg/dL and CPR 5.30 ng/dL with 750 mg metformin, 10 mg gliclazide and 18 U insulin glargine. Transient, but total cessation of insulin secretion was documented in a patient with type 2 diabetes under severe metabolic decompensation. Swift, sustained recovery of insulin release indicated that lack of insulin at the time of emergency was due to secretory failure, i.e., unresponsive exocytotic machinery or depletion of releasable insulin, rather than loss of beta cells.

Prediabetes defined by the International Expert Committee as a risk for development of glomerular hyperfiltration.

AIMS: 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). METHODS: 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) < 60 ml/min/1.73 m2 and/or dipstick-positive proteinuria, and GH by upper 95th eGFR in the Japanese adults. PrediabetesIEC was diagnosed by "HbA1c 42-46 mmol/mol and/or FPG 6.1-6.9 mmol/L", PrediabetesADA by "HbA1c 39-46 mmol/mol and/or FPG 5.6-6.9 mmol/L", PrediabetesADA-IEC for the condition met the ADA but not the IEC prediabetes definition, and the ADA-normal glucose regulation (NGRADA) by both HbA1c and FPG lower than PrediabetesADA. Risk of PrediabetesIEC and PrediabetesADA for incident GH was examined by multivariate Cox proportional hazards model with seven covariates and probability of incident GH was calculated on the basis of it. RESULTS: PrediabetesIEC was a significant risk for incident GH [adjusted HR 1.91, 95% CI 1.32-2.71] but PrediabetesADA was not [adjusted HR 1.22, 95% CI 0.93-1.61]. The mean (SD) probability of incident GH was 2.3 (4.5)%, 1.0 (2.3)% and 1.0 (2.4)% for PrediabetesIEC, PrediabetesADA-IEC and NGRADA, respectively: the former was significantly larger than the latter two which were not significantly different from each other. CONCLUSIONS: PrediabetesIEC was an independent risk for incident GH.

Reappraisal of attenuated insulin sensitivity in the evolution of non-alcoholic fatty liver disease.

BACKGROUND/OBJECTIVES: 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. SUBJECTS/METHODS: 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 < 0.01). Fatty liver (FL) was diagnosed by ultrasonography and diabetes by fasting plasma glucose (FPG) ≥ 7 mmol/L and/or glycohemoglobin A1c ≥ 6.5%. Multinominal comparison was performed with incident FL (FLw/oDM, n = 486), diabetes (DMw/oFL, n = 171), and FL plus diabetes (FL/diabetes, n = 58) as targets; none of the above (n = 4,138) was the control. SPISE was taken as a predictor with adjustment for covariates. Trajectory of SPISE during the 5 years before development of each condition was also assessed. RESULTS: With SPISE tertile 3 (>10.06) as the reference, tertile 1 (<8.07) was related to incident FLw/oDM and FL/diabetes with OR (95% CI) 3.47 (2.60-4.63) and 1.78 (1.10-2.87), respectively, and tertile 2 (8.07-10.06) related to FLw/oDM with OR (95% CI) 1.38 (1.03-1.85). Low SPISE was not significantly related to incident diabetes. At -5 years, SPISE was 12% (P < 0.05) and 13% (P < 0.01) lower in those developed FLw/oDM and FL/diabetes, respectively, than the control. At year 0, SPISE in the two groups was 18% and 21% lower than the control, respectively (P < 0.01). CONCLUSIONS: Attenuation of Si indexed by SPISE was a risk factor for NAFLD.

Elevated haemoglobin A1c but not fasting plasma glucose conveys risk of chronic kidney disease in non-diabetic individuals.

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) < 60 ml/min/1.73 m2 and/or dipstick proteinuria. Cox proportional hazards model was applied with sex, age, insulin sensitivity, systolic blood pressure, eGFR and serum alanine aminotransferase level as covariates. 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.

Pharmacokinetics of insulin disappearance after massive overdosing.

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.

Type 2 Diabetes: When Does It Start?

OBJECTIVE: We aimed to clarify the onset of diabetes. DESIGN: Data from 27,392 nondiabetic health examinees were retrospectively analyzed for a mean of 5.3 years. Trajectories of fasting plasma glucose (FPG), body mass index (BMI), and the single point insulin sensitivity (Si) estimator (SPISE), an index of Si, 10 years before diagnosis of prediabetes (PDM; n = 4781) or diabetes (n = 1061) were separately assessed by a mixed effects model. Diabetes and PDM were diagnosed by the American Diabetes Association definition on the basis of FPG and glycosylated hemoglobin A1c values. RESULTS: In individuals who developed diabetes, mean FPG and BMI were significantly higher (P < 0.01 each) and SPISE lower than those who did not at -10 years: FPG 101.5 mg/dL vs 94.5 mg/dL, BMI 24.0 kg/m2 vs 22.7 kg/m2, and SPISE 7.32 vs 8.34, P < 0.01 each. These measurements, in subjects who developed prediabetes, were slightly but definitely different from those who did not, already at -10 years: FPG 91.8 mg/dL vs 89.6 mg/dL, BMI 22.6 kg/m2 vs 22.1 kg/m2, and SPISE 8.44 vs 8.82, P < 0.01 each. In both cases, the differences were progressively greater toward year 0, the time of diabetes, or PDM diagnosis. CONCLUSIONS: FPG was significantly elevated in those who developed diabetes at least 10 years before diagnosis of diabetes, and this was also the case in those who developed PDM. Glucose dysregulation precedes diagnosis of diabetes at least for 20 years.

Postchallenge hyperglycemia in subjects with low body weight: implication for small glucose volume.

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.

Primacy of lowered baseline glomerular filtration rate as a risk for incident chronic kidney disease: A longitudinal study in Japanese subjects.

AIM: 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. METHODS: Consecutive 171 536 health examinees (median age 49 years and estimated glomerular filtration rate (eGFR) 78.2 mL/min per 1.73 m2 ) without CKD were re-examined after a median period of 6.2 years. Results of Cox proportional hazards models in randomly assigned two thirds (Derivation cohort) were verified in the rest (Validation cohort). CKD was defined as eGFR <60 mL/min per 1.73 m2 or positive dipstick proteinuria. RESULTS: In 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 eGFR <70 mL/min per 1.73 m2 was as high as 90.1. Performance of prediction of CKD by the probability on the basis of the seven risk factors combined was only marginally preferable to eGFR alone. The area under the receiver operating characteristic curve (95% CI) for the prediction was 0.846 (0.826-0.864) and 0.822 (0.802-0.840) (P < 0.01), the kappa statistic was 0.263 and 0.250 (n.s.), and the mean absolute difference between "predicted probability" and "observed" CKD was 1.4% and 1.9% (P = 0.14) by the combined model and eGFR alone, respectively. CONCLUSION: Seven 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.

A Case of Hypocalcaemia Due to Vitamin D Deficiency in 'Hikikomori' Syndrome.

OBJECTIVE: To describe hypocalcaemia due to vitamin D deficiency in 'hikikomori' syndrome. MATERIALS AND METHODS: A 37-year-old man with 'hikikomori' syndrome for a year was admitted with hypocalcaemia (serum ionic calcium 1.17 mmol/l). Serum 1,25(OH)2-vitamin D3 determined by liquid chromatography-tandem mass spectrometry was depressed at 12.1 pg/ml (29.0 pmol/l) and plasma intact PTH elevated at 324 ng/l. Administration of 1 µg/day 1α(OH)-vitamin D3 and 1 g/day calcium lactate for 1 week normalized calcium and PTH, and raised 1,25(OH)2-vitamin D3 to low normal levels. CONCLUSION: This is the first report of hypocalcaemia due to vitamin D deficiency in a patient with 'hikikomori' syndrome. LEARNING POINTS: A patient with psychiatric disorders can develop endocrine/metabolic abnormality.Hikikomori syndrome should be listed as a possible cause of hypocalcaemia in adults.Early diagnosis of hypocalcaemia in hikikomori syndrome prevents bone damage.