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.

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.

Fulminant type 1 diabetes with robust recovery of insulin secretion: a case report.

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.

Elevation of thyrotropin upon accidental hypothermia in an elderly man.

BACKGROUND: 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. PATIENT FINDINGS: 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 to >36°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." SUMMARY: 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. CONCLUSIONS: 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.

Systematic analysis of risk factors for coronary heart disease in Japanese patients with type 2 diabetes: a matched case-control study.

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.

Index of glucose effectiveness derived from oral glucose tolerance test.

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 SgI(O) 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 log(10)DI(O) and 2-h post-glucose plasma glucose at OGTT (2hPG) in each glucose tolerance category: DI(O) denotes oral disposition index, a product of the Matsuda Index and δIRI(0-30)/δPG(0-30). Thirdly, expected 2hPG (2hPG(E)) of a given subject was obtained from the regression, and the ratio of 2hPG to 2hPG(E) (2hPG/2hPG(E)) was determined as an adjustment factor. Lastly, SgI(O) ([mg/dl]/min) was calculated as [PPG-without insulin and Sg]-[PPG-without insulin / with Sg] x [(2hPG) / 2hPG(E)]. SgI(O) 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. SgI(O) 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, SgI(O) 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, SgI(O) could be a simple, quantitative index for Sg.

Paradoxical surge of corticotropin after glucocorticoid replacement in central adrenal insufficiency.

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.