Retrospective cohort study to examine the association between serum amylase and the incidence of type 2 diabetes mellitus, Toranomon Hospital Health Management Center Study 23 (TOPICS 23).

INTRODUCTION: Low serum amylase values are cross-sectionally associated with the prevalence of type 2 diabetes mellitus (T2DM) but have not been shown to be longitudinally associated with its incidence. This retrospective cohort (ie, historical cohort) study aimed to examine the association of previously lowered levels of serum amylase with incident T2DM. RESEARCH DESIGN AND METHODS: Examined were 8316 individuals who had annual health examinations for 6 years (ie, 7 times) at the Toranomon Hospital Health Management Center. The trajectory of serum amylase as the study exposure was classified into two elements: (1) serum amylase level at entry and (2) change in serum amylase, which was expressed as the annual change rate. The annual change rate was calculated by dividing the change in the amylase values according to follow-up periods. Regression analyses were performed to examine the association between low and decreased levels of serum amylase and the incidence of T2DM. RESULTS: Analyzed were 6917 individuals who had not developed T2DM within 1 year after cohort entry. T2DM thereafter occurred in 1021 patients. Cox regression indicated that the adjusted HR (95% CI) for incident T2DM for amylase ≤57 IU/L (quintile (Q) 1) was 0.97 (0.84 to 1.13) compared with amylase ≥58 IU/L (Q2-Q5). Logistic regression indicated that the adjusted OR (95% CI) for an annual change rate of amylase ≤-2.0% (Q1) vs ≥-1.9% (Q2-Q5) was 3.53 (3.00 to 4.16). The adjusted ORs were consistently significant throughout sensitivity analyses according to baseline amylase and the combination of age, body mass index, and hemoglobin A1c. CONCLUSIONS: Results showed that not low but previously decreased serum amylase was a risk factor for T2DM, suggesting the significance of periodic examinations of serum amylase values to detect individuals at high risk of T2DM.

Independent risk factors of rapid glomerular filtration rate decline in patients with type 2 diabetes with preserved kidney function and normoalbuminuria: A multicenter cohort study.

AIMS/INTRODUCTION: Research on the incidence and underlying mechanisms of rapid renal function decline in patients with type 2 diabetes mellitus with preserved renal function and normoalbuminuria is limited. This study aimed to investigate the involvement of hemoglobin level as a risk factor for rapid decliners among patients with type 2 diabetes with preserved renal function and normoalbuminuria. MATERIALS AND METHODS: This was a retrospective observational study of 242 patients with type 2 diabetes with a baseline estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 and normoalbuminuria (<30 mg/gCr), followed up for >1 year. The annual rate of estimated glomerular filtration rate decline during the follow-up period was calculated using least square regression analysis; rapid decliners defined at ≥3.3%/year. Risk factors associated with rapid decliners were identified using a logistic regression analysis of variables previously identified as risk factors of rapid decliners. RESULTS: The median follow-up period was 6.7 years, and 34 patients showed rapid decliners. On multivariate analysis, lower baseline hemoglobin level was a risk factor of rapid decliners (odds ratio 0.69, 95% confidence interval 0.47-0.99; P = 0.045). Furthermore, the baseline hemoglobin levels were correlated positively with iron and ferritin levels, implying that an impaired iron metabolism might cause lower hemoglobin levels in rapid decliners. CONCLUSIONS: In patients with type 2 diabetes with preserved renal function and normoalbuminuria, lower hemoglobin levels were a risk factor for rapid decliners, where disturbed iron metabolism might precede the development of diabetic kidney disease.

Association between Hypokalemia and Albuminuria in a Japanese General Population.

INTRODUCTION: Hypokalemia is associated with an increased risk of chronic kidney disease (CKD) and is a risk factor for mortality. Albuminuria is an early manifestation of CKD. We investigated the association between hypokalemia and the prevalence of albuminuria in a Japanese general population. METHODS: We analyzed the data of 18,289 subjects who underwent annual health checkups in 2018. We categorized them into four groups according to their concentration of serum potassium (sK) and performed a multivariate logistic regression analysis to determine the association between hypokalemia and the prevalence of albuminuria in this population. Hypokalemia was defined as having an sK = 3.1-3.5 mEq/L. After dividing the subjects into those with/without renal dysfunction, those with/without hypertension, and those with/without hyperglycemia, we examined the association between hypokalemia and albuminuria in each group. RESULTS: Compared to the subjects with sK = 4.1-4.5 mEq/L, the subjects with hypokalemia had a significantly high prevalence of albuminuria: multivariable-adjusted odds ratio (OR) = 2.70 (95% confidence interval [CI] 1.84-3.96). The subgroup analyses showed the following multivariable-adjusted ORs (95% CIs) of the subjects: without renal dysfunction, 3.08 (2.00-4.73); with renal dysfunction, 2.05 (0.89-4.69); without hypertension, 2.89 (1.36-6.16); with hypertension, 2.60 (1.67-4.04); without hyperglycemia, 2.49 (1.62-3.84); and with hyperglycemia, 3.55 (1.43-8.79). CONCLUSIONS: Hypokalemia was significantly associated with the high prevalence of albuminuria in general population. Regardless of the presence/absence of renal dysfunction, hypertension, or hyperglycemia, hypokalemia was positively associated with the prevalence of albuminuria, and the associations were significant except for the subjects with renal dysfunction.

Association between Helicobacter pylori infection, eradication and diabetes mellitus.

AIMS/INTRODUCTION: It is suspected that Helicobacter pylori is associated with extradigestive diseases including diabetes. So far, a number of studies have examined the association between H. pylori and diabetes, and the results were conflicting. The aim of the present study was to examine the association between H. pylori infection, eradication and diabetes. MATERIALS AND METHODS: The present cross-sectional study was carried out using data from annual health checkups carried out at the Toranomon Hospital Health Management Center. The status of H. pylori infection, determined by serum antibodies and history of eradication, was categorized into three groups as "never," "current" and "past." The association between H. pylori infection and diabetes was examined using logistic regression. RESULTS: Of 21,634 participants, 6,530 (30.2%) had a current or past history of H. pylori infection, and 1,184 (5.5%) were identified as having diabetes. Multivariate adjusted odds ratios for diabetes compared with the "never" group were 1.36 (95% confidence interval 1.10-1.67) for the "current" group and 0.92 (95% confidence interval 0.79-1.07) for the "past" group. The association between H. pylori infection and diabetes was also observed among participants without a history of eradication. CONCLUSIONS: We found that current H. pylori infection was associated with an increased risk of diabetes, and the increased risk was not observed among participants after eradication. The results were concordant with the hypothesis that H. pylori infection increases the risk of diabetes. Further studies are necessary to validate the present results.

Urinary afamin levels are associated with the progression of diabetic nephropathy.

AIMS: In this study, we applied quantitative proteomic analysis to identify urinary proteins associated with diabetic nephropathy (DN). METHODS: Two-dimensional image-converted analysis of liquid chromatography and mass spectrometry detected the proteins differentially excreted between normoalbuminuric and macroalbuminuric patients with type 2 diabetes mellitus (T2DM) (n = 6 each). Urinary levels of excreted proteins were measured by multiple reaction monitoring (MRM) analysis using an independent sample set (n = 77). Urinary afamin levels were measured by ELISA in T2DM and DN patients enrolled in this cohort study (n = 203). RESULTS: One-hundred-four proteins displayed significant alterations in excretion. Nine of these candidates were validated by MRM analysis. Among them, the levels of afamin, CD44 antigen, and lysosome-associated membrane glycoprotein 2, which have not previously been implicated in DN, were significantly associated with both the urinary albumin to creatinine ratio (ACR) and eGFR. We further measured afamin levels in urine collected from T2DM patients who did not yet have significant kidney disease (ACR < 300 mg/g or eGFR change rate ≤ 3.3%/year). The urinary afamin to creatinine ratio (Afa/Cre) was significantly higher in patients who progressed to a more severe DN stage or had early renal decline than in patients who did not. CONCLUSIONS: Afa/Cre was significantly increased in T2DM patients who subsequently developed DN. Afa/Cre may be useful to predict patients with T2DM at high risk of nephropathy before the development of macroalbuminuria or reduced kidney function, although further validation studies in a larger population are needed.

Changes in Antidiabetic Drug Prescription and Glycemic Control Trends in Elderly Patients with Type 2 Diabetes Mellitus from 2005-2013: An Analysis of the National Center Diabetes Database (NCDD-03).

Objective To analyze the changes in the pharmacotherapy and glycemic control trends in elderly patients with type 2 diabetes mellitus (T2DM) in Japan. Methods We extracted the data of 7,590 patients (5,396 men and 2,194 women; median year of birth: 1945) with T2DM registered in the National Center Diabetes Database for the years 2005 to 2013, and conducted age-stratified (<65, 65-74, and ≥75 years of age) analyses. Results The hemoglobin A1c (HbA1c) levels declined from 2005 to 2013, and for those who received antihyperglycemic drug prescription, the HbA1c levels were lower in the older age group than in the younger age group. In the ≥75 age group, dipeptidyl peptidase-4 inhibitors (DPP4i) became the most frequently prescribed drug (49.1%) in 2013, and sulfonylureas remained the second-most frequently prescribed drug (37.8%) with decreased prescribed doses. The prescription ratio of oral drugs associated with a risk of hypoglycemia was higher in patients ≥75 years of age than in those <75 years of age (40.5% and 26.4%, respectively in 2013), although it showed a downward trend. The prescription rates of insulin for patients ≥75 years of age increased during the study period. Conclusion The pharmacotherapy trends for elderly patients with T2DM changed dramatically in Japan with the launch of DPP4i in 2009. Glycemic control in a considerable portion of the ≥75 age group in Japan was maintained at the expense of potential hypoglycemia by the frequent, although cautious, use of sulfonylureas, glinides and insulin.

Postprandial Glucose Surges after Extremely Low Carbohydrate Diet in Healthy Adults.

Carbohydrate-restricted diets are prevalent not only in obese people but also in the general population to maintain appropriate body weight. Here, we report that extreme carbohydrate restriction for one day affects the subsequent blood glucose levels in healthy adults. Ten subjects (median age 30.5 years, BMI 21.1 kg/m2, and HbA1c 5.5%), wearing with a continuous glucose monitoring device, were given isoenergetic test meals for 4 consecutive days. On day 1, day 2 (D2), and day 4 (D4), they consumed normal-carbohydrate (63-66% carbohydrate) diet, while on day 3, they took low-carbohydrate/high-fat (5% carbohydrate) diet. The daily energy intake was 2,200 kcal for males and 1,700 kcal for females. On D2 and D4, we calculated the mean 24-hr blood glucose level (MEAN/24h) and its standard deviation (SD/24h), the area under the curve (AUC) for glucose over 140 mg/dL within 4 hours after each meal (AUC/4h/140), the mean amplitude of the glycemic excursions (MAGE), the incremental AUC of 24-hr blood glucose level above the mean plus one standard deviation (iAUC/MEAN+SD). Indexes for glucose fluctuation on D4 were significantly greater than those on D2 (SD/24h; p = 0.009, MAGE; p = 0.013, AUC/4h/140 after breakfast and dinner; p = 0.006 and 0.005, and iAUC/MEAN+SD; p = 0.007). The value of MEAN/24h and AUC/4h/140 after lunch on D4 were greater than those on D2, but those differences were not statistically significant. In conclusion, consumption of low-carbohydrate/high-fat diet appears to cause higher postprandial blood glucose on subsequent normal-carbohydrate diet particularly after breakfast and dinner in healthy adults.

Cross-Over Study Comparing Postprandial Glycemic Increase After Addition of a Fixed-Dose Mitiglinide/Voglibose Combination or a Dipeptidyl Peptidase-4 Inhibitor to Basal Insulin Therapy in Patients with Type 2 Diabetes Mellitus.

BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6%; fat, 43.2%). Self-monitoring blood glucose levels were measured at 0, 30, 60, and 120 min after the meal tests, and the increase in the postprandial area under the curve (AUC)0-120 min was determined. The HbA1c, glycated albumin, and 1,5-anhydroglucitol (AG) levels were measured, and continuous glucose monitoring was performed. RESULTS The increase in the postprandial AUC0-120 min was significantly smaller in the M+V group than in the L group after both meals. The 24-h average, 24-h standard deviations, 24-h AUC, and mean amplitude of glycemic excursion (MAGE) were similar for both groups and after both meals. The change in 1,5-AG was higher in the M+V group than in the L group. CONCLUSIONS The combination of M+V with basal therapy improved postprandial glucose excursion more effectively than L in T2DM patients.

A positive family history of hypertension might be associated with an accelerated onset of type 2 diabetes: Results from the National Center Diabetes Database (NCDD-02).

Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.

Proteomic analysis of serum biomarkers for prediabetes using the Long-Evans Agouti rat, a spontaneous animal model of type 2 diabetes mellitus.

AIMS/INTRODUCTION: To identify candidate serum molecules associated with the progression of type 2 diabetes mellitus, differential serum proteomic analysis was carried out on a spontaneous animal model of type 2 diabetes mellitus without obesity, the Long-Evans Agouti (LEA) rat. MATERIALS AND METHODS: We carried out quantitative proteomic analysis using serum samples from 8- and 16-week-old LEA and control Brown Norway (BN) rats (n = 4/group). Differentially expressed proteins were validated by multiple reaction monitoring analysis using the sera collected from 8-, 16-, and 24-week-old LEA (n = 4/each group) and BN rats (n = 5/each group). Among the validated proteins, we also examined the possible relevance of the human homolog of serine protease inhibitor A3 (SERPINA3) to type 2 diabetes mellitus. RESULTS: The use of 2-D fluorescence difference gel electrophoresis analysis and the following liquid chromatography-multiple reaction monitoring analysis showed that the serum levels of five proteins were differentially changed between LEA rats and BN rats at all three time-points examined. Among the five proteins, SERPINA3N was increased significantly in the sera of LEA rats compared with age-matched BN rats. The serum level of SERPINA3 was also found to be significantly higher in type 2 diabetes mellitus patients than in healthy control participants. Furthermore, glycated hemoglobin, fasting insulin and estimated glomerular filtration rate were independently associated with the SERPINA3 levels. CONCLUSIONS: These findings suggest a possible role for SERPINA3 in the development of the early stages of type 2 diabetes mellitus, although further replication studies and functional investigations regarding their role are required.

Reduced serum level of leukocyte cell-derived chemotaxin 2 is associated with the presence of diabetic retinopathy.

BACKGROUND: Vascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR. METHODS: The study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR. Serum LECT2 levels were measured using an enzyme-linked immunosorbent assay. Data were evaluated using Spearman's rank correlation, univariate and multivariate logistic regression. RESULTS: Serum LECT2 levels were significantly lower in participants with DM having DR than in those not having DR (35.6±14.9ng/ml vs. 44.5±17.6ng/ml, P<0.001). Spearman's rank correlation analysis revealed a significant association between serum LECT2 levels and the presence of DR (P<0.001). Multiple regression analysis revealed that serum LECT2 levels were independently related to DR (P<0.001). CONCLUSIONS: These findings indicated that serum LECT2 level is negatively associated with the presence of DR and suggest that low circulating LECT2 level is a risk factor for DR.

Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22.

Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension.

Beneficial effects through aggressive coronary screening for type 2 diabetes patients with advanced vascular complications.

Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ≥70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P < 0.001) and 48.4% vs 9.3% (P < 0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients with advanced vascular complications reduced cardiovascular death and nonfatal cardiovascular events.

Body mass index and the risk of cancer incidence in patients with type 2 diabetes in Japan: Results from the National Center Diabetes Database.

AIMS/INTRODUCTION: Both type 2 diabetes and obesity increase the risk of some types of cancers, and underlying mechanisms are thought to be, at least in part, common. In the present study, we carried out a retrospective cohort study of the relationship between body mass index (BMI) categories and cancer development in Japanese type 2 diabetic patients. MATERIALS AND METHODS: A total of 113 incident cancers including 35 cancers whose incidence was reported to be increased by obesity (27 colorectal cancers, two breast cancers in postmenopausal women, one endometrial cancer, four renal cancers and one gallbladder cancer) were identified in 2,334 type 2 diabetic patients (1,616 men and 718 women) over an average observation period of 5.1 years. RESULTS: In men, there was no significant association between the BMI categories at the start of the observation period and the development of any cancer. In contrast, the incidence of all of the cancers in the women was significantly higher in the group with a BMI of less than 22.0 kg/m2 (hazard ratio 3.07, 95% CI 1.01-9.36). In either sex, there was no significant relationship between the BMI categories and the development of cancers whose risk is known to be increased by obesity. CONCLUSIONS: The findings of the present study were limited by the relatively small number of patients in the cohort, which posed a danger of not finding significance. However, the results suggested that obesity did not become an additional risk factor for cancer in Japanese type 2 diabetic patients.

Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors.

AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal (GI) organic diseases. METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre-colonoscopy, 9 symptoms (borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test-retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank-ordered logistic model adjusted for related confounders, and odds ratios (ORs) were estimated. RESULTS: In multivariate analysis, constipation [adjusted odds ratio (AOR) = 1.57, CI: 1.33-1.85, P < 0.01] and hard stools (AOR = 1.56, CI: 1.33-1.84, P < 0.01) were associated with diabetes, and fecal urgency (AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation (AOR = 1.16, CI: 1.00-1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good (mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with HbA1c ≥ 8.0% (AOR = 2.11, CI: 1.19-3.73), body mass index (BMI) < 25 (AOR = 2.11, CI: 1.22-3.66), and insulin use (AOR = 1.90, CI: 1.08-3.36); hard stools with diabetes duration (AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI < 25 (AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI < 25 (AOR = 2.60, CI: 1.52-4.43), serum creatinine level (AOR = 1.27, CI: 1.10-1.47), and insulin use (AOR = 1.92, CI: 1.09-3.38). CONCLUSION: Diabetes is associated with constipation, hard stools, fecal urgency, and incomplete evacuation, and poor glycemic control, duration, leanness, and nephropathy affect the risk of these symptoms.

Accelerated decline of renal function in type 2 diabetes following severe hypoglycemia.

AIMS: This study aimed to evaluate whether the pronounced elevation in blood pressure during severe hypoglycemia is associated with subsequent renal insufficiency. METHODS: We conducted a 3-year cohort study to assess the clinical course of renal function in type 2 diabetes patients with or without blood pressure surge during severe hypoglycemia. RESULTS: Of 111 type 2 diabetes patients with severe hypoglycemia, 76 exhibited an extremely high systolic blood pressure before treatment, whereas 35 demonstrated no such increase (179.1 ± 27.7 mmHg vs. 131.1 ± 20.2 mmHg, P<0.001). At 12h after treatment, systolic blood pressure did not differ significantly (131.5 ± 30.7 mmHg vs. 123.5 ± 20.7 mmHg; P=0.39). The estimated glomerular filtration rate (GFR) before and at the time of severe hypoglycemia did not significantly differ between both groups. A multivariate Cox proportional hazards regression analysis revealed that blood pressure surge during severe hypoglycemia was independently associated with a composite outcome of a more than 15 mL/min/1.73 m(2) decrease in the estimated GFR and initiation of chronic dialysis (hazard ratio, 2.68; 95% confidence interval, 1.12-6.38; P=0.02). CONCLUSIONS: Renal function after severe hypoglycemia was significantly worse in type 2 diabetes patients with blood pressure surge during severe hypoglycemia than those without blood pressure surge.

Effectiveness of Prior Use of Beta-Blockers for Preventing Adverse Influences of Severe Hypoglycemia in Patients With Diabetes: An Observational Study.

The study aimed to identify predictors of severe acute hypertension (≥ 180/110 mmHg) during severe hypoglycemia and to assess the efficacy of prior use of catecholamine-blocking agents for preventing adverse influences in diabetic patients with severe hypoglycemia. We performed a retrospective study between January 2006 and March 2012 to assess diabetic patients with severe hypoglycemia at a single center in Japan. Severe hypoglycemia was defined as the presence of any hypoglycemic symptoms that required the medical assistance of another person after visiting the emergency room by ambulance. Multivariate logistic regression analysis was performed to identify possible predictors of severe hypertension due to severe hypoglycemia and to assess whether prior use of alpha- or beta-blockers is beneficial for the prevention of severe hypertension in diabetic patients with severe hypoglycemia. Multivariate adjustments were made for age, sex, preexisting hypertension, history of ischemic heart disease, blood glucose level upon arrival, estimated GFR, and prior use of alpha- or beta-blockers. A total of 59,602 patients who visited the emergency room were screened and 352 diabetic patients with severe hypoglycemia were enrolled. Incidences of severe hypertension before and at 3 and 6 hours after the initiation of antihypoglycemic treatment were 21.3%, 6.7%, and 0% in patients with type 1 diabetes (n = 61) and 38.8%, 18.2%, and 8.2% in patients with type 2 diabetes (n = 291), respectively. Aging was positively (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00-1.03; P = 0.02) and female sex was negatively (OR, 0.50; 95% CI, 0.29-0.86; P = 0.01) associated with occurrence of severe hypertension during severe hypoglycemia. In addition, prior use of beta-blockers was negatively associated with occurrence of severe hypertension during severe hypoglycemia using multivariate logistic regression analysis (OR, 0.31; 95% CI, 0.11-0.83; P = 0.02). None of the patients with prior use of beta-blockers had hypokalemia (<3.0 mEq/L). Prior use of beta-blockers may prevent adverse influences such as severe hypertension and hypokalemia during severe hypoglycemia in diabetic patients.

Acute Multiple Arteriovenous Thromboses in a Patient with Diabetic Ketoacidosis.

Diabetic ketoacidosis (DKA) is one of the most serious acute complications of diabetes mellitus. An arterial thrombotic tendency from DKA is relatively common; however, the occurrence of acute multiple arteriovenous thromboses is rare. We herein report the case of a 49-year-old man with DKA complicated by multiple thromboses. After transfer to our emergency room with DKA, the patient developed sudden abdominal pain. Contrast-enhanced computed tomography revealed near-complete occlusion of the superior mesenteric artery, superior mesenteric vein, splenic artery, and right femoral artery. This occurrence highlights the need for considering the risk of thrombosis during the initial treatment for DKA.

High risk of abnormal QT prolongation in the early morning in diabetic and non-diabetic patients with severe hypoglycemia.

BACKGROUND: Several studies have suggested that the occurrence of severe hypoglycemia during sleep may be more dangerous for cardiac arrhythmia than that in the day-time. METHODS: We performed a retrospective study between January 2006 and March 2012 to assess electrocardiograms during severe hypoglycemia in patients with or without diabetes. RESULTS: A total of 59,602 patients who visited the emergency room by ambulance were screened, and 287 patients with severe hypoglycemia were enrolled. The median blood glucose levels in patients with (DM, n = 192) and without diabetes (non-DM, n = 95) were 30 and 45 mg/dL, respectively. During severe hypoglycemia, the incidence of abnormal QT prolongation was significantly higher in the early morning (4-10 a.m.) than at other times (DM group, 74.3% versus 54.1%, P = 0.02; non-DM group, 78.3% versus 50.0%, P = 0.01). Multivariate logistic regression analysis identified the occurrence of severe hypoglycemia in the early morning as a strong factor for abnormal QT prolongation (DM group, odds ratio [OR] 2.80, 95% confidence interval [CI] 1.15-6.80, P = 0.02; non-DM group, OR 4.53, 95% CI 1.30-15.74, P = 0.01). CONCLUSIONS: The incidence of abnormal QT prolongation during severe hypoglycemia was significantly higher in the early morning than at all other times, independent of the cause of severe hypoglycemia.