Shintaro Okamura

Localized Amyloidosis at the Site of Repeated Insulin Injection in a Patient With Type 2 Diabetes

We present the case of a 69-year-old woman with type 2 diabetes mellitus who developed severe insulin resistance associated with insulin injections into a subcutaneous mass formed by repeated injections into the same site over many years. The patient (height, 150 cm; weight, 79 kg; BMI, 35.1 kg/m2) was admitted to Tenri Hospital with severe insulin resistance. She was undergoing insulin therapy since 56 years of age. Her glycemic control was fair until 63 years of age, after which it worsened and necessitated an increase in her insulin dose. This led to a 15-kg increase in body weight. On admission, her insulin regimen comprised a single injection of 33 units of neutral protamine Hagedorn insulin at bedtime and three daily injections of 33 units of premixed human insulin (70/30) before each meal. …

Prevalence of Cardiovascular Disease and Its Risk Factors in Primary AldosteronismNovelty and Significance: A Multicenter Study in Japan

There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K+ ⩽3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations <125 pg/mL. Thus, patients with PA seem to be at a higher risk of developing CVD than patients with essential hypertension. Moreover, patients with PA presenting with hypokalemia, the unilateral subtype, or plasma aldosterone concentration ≥125 pg/mL are at a greater risk of CVD and have a greater need for PA-specific treatments than others.

Duration of diabetes and types of diabetes therapy in Japanese patients with type 2 diabetes: The Japan Diabetes Complication and its Prevention prospective study 3 (JDCP study 3)

To analyze the association between the duration of diabetes and selection of diabetes therapy in a large database of Japanese patients with type 2 diabetes.

Predictor variables and an equation for estimating HbA1c attainable by initiation of basal supported oral therapy.

Aims/Introduction:  A method of estimating HbA1c attained after initiation of basal supported oral therapy (BOT) has not been reported previously. The aim of the present study was to determine which characteristics of patients could influence the effectiveness of BOT introduction, and to obtain an equation to estimate HbA1c after BOT initiation.

Serum uric acid levels are associated with increased risk of newly developed diabetic retinopathy among Japanese male patients with type 2 diabetes: A prospective cohort study (diabetes distress and care registry at Tenri [DDCRT 13])

We assessed the prospective association between baseline serum uric acid levels and consequent risk of developing diabetic retinopathy.

Correlation Between Lateralization Index of Adrenal Venous Sampling and Standardized Outcome in Primary Aldosteronism

Abstract Objectives The aim of this study was to investigate the impact of adrenal venous sampling (AVS) lateralization cutoffs on surgical outcomes. Patients and Methods Cosyntropin-stimulated AVS was used to guide surgical management of 377 patients with primary aldosteronism (PA) who were evaluated 6 months after surgery. Main Outcome Measures The proportion of patients that achieved clinical benefit and complete biochemical success based on the AVS aldosterone lateralization index (LI) was determined. Results Clinical benefit was achieved in 29 of 47 patients with an LI between 2 and 4, in 66 of 101 with an LI between 4 and 10, and in 158 of 203 with an LI > 10 (P < 0.01 for trend). Complete biochemical success was achieved in 27 of 42 with an LI between 2 and 4, in 60 of 76 with an LI between 4 and 10, and in 127 of 155 with an LI > 10 (P = 0.024 for trend). After adjustment for confounders and using those patients with an LI between 2 and 4 as a reference, a clinical benefit was associated only with those with an LI > 10 (OR, 2.30; 95% CI, 1.03 to 5.16), whereas complete biochemical success was associated with those with an LI between 4 and 10 (OR, 2.83; 95% CI, 1.14 to 7.01) or LI > 10 (OR, 3.55; 95% CI, 1.47 to 8.55). Conclusions Difference of clinical outcome was relatively small when strict LI diagnostic threshold was used; biochemical cure was sufficiently achieved when an LI > 4 was used. Our study by standardized outcome measures validated that an LI > 4 may be appropriate for determining unilateral disease in PA.

Real-life glycemic control in patients with type 2 diabetes treated with insulin therapy: A prospective, longitudinal cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT 9])

We investigated the association between four insulin regimens, and increase in glycated hemoglobin (HbA1c) and insulin dose in a real‐life clinical setting because there are no data about them among insulin regimens.

Association of proton pump inhibitor use with the risk of the development or progression of albuminuria among Japanese patients with diabetes: A prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 16)]

AIMS We aimed to determine the prospective association between proton pump inhibitor (PPI) use and the subsequent risk of the development or progression of albuminuria or eGFR. METHODS Longitudinal data of patients with diabetes were obtained from a large Japanese diabetes registry. To assess the independent correlation between PPI use and the development or progression of urine microalbuminuria, the time-varying Cox proportional hazards model was used with adjustment for potential confounders. RESULTS The mean patient age, body-mass index (BMI), and hemoglobin A1c (HbA1c) levels were 65.7 y, 24.5 kg/m2, and 7.5% (57.9 mmol/mol), respectively. In 1711 patients without albuminuria, we observed 599 cases with development of albuminuria over median follow-up of 4.0 years, and in 1279 patients with microalbuminuria, 290 cases with urinary albuminuria progression over 4.0 years, and 257 eGFR decline cases over 3.8 years. PPI use was not associated with the development of albuminuria (HR = 0.88; 95%CI, 0.77-1.01; p = .058), progression of albuminuria (HR = 1.24; 95%CI, 0.87-1.79; p = .236), nor eGFR decline (HR = 1.05; 95%CI, 0.81-1.34; p = .973) even in a propensity score-adjusted model with time-varyingly updating PPI use information. CONCLUSIONS In conclusion, PPI use was not associated with the subsequent risk of development or progression of albuminuria, or eGFR decline in patients with diabetes.

Higher levels of physical activity are independently associated with a lower incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: A prospective cohort study, Diabetes Distress and Care Registry at Tenri (DDCRT15)

We assessed the prospective association between baseline levels of physical activity (PA) and the incidence of newly developed diabetic retinopathy (DR) in patients with type 2 diabetes. Data from 1,814 patients with type 2 diabetes without DR were obtained from a Japanese diabetes registry at Tenri Hospital, Nara, Japan. To assess the independent correlations between baseline PA levels and newly developed DR, the participants were divided into five categories based on their PA levels. A Cox proportional hazards model with time-varying exposure information was used and adjusted for potential confounders to assess the independent correlations. At baseline, the mean age, BMI, and hemoglobin A1c levels of the patients were 65.5 years, 24.5 kg/m2, and 7.2% (54 mmol/mol), respectively. After 2 years, newly developed DR was confirmed in 184 patients (10.1%). Patients with newly developed DR had longer duration of type 2 diabetes (14.7 versus 11.0 years, p < 0.0001), higher systolic blood pressure (139.2 versus 135.1 mmHg, p = 0.0012), lower estimated glomerular filtration rate (74.0 versus 77.1 mL/min/1.73 m2, p = 0.0382), greater urinary albumin–creatinine ratio (4.00 versus 2.45 mg/mmol, p < 0.0039), and higher HbA1c levels (7.5 versus 7.2%, p = 0.0006) than those without newly developed DR. The multivariable-adjusted hazard ratios for DR development were 0.87 (95% CI, 0.53–1.40; p = 0.557), 0.83 (95% CI, 0.52–1.31; p = 0.421), 0.58 (95% CI, 0.35–0.94; p = 0.027), and 0.63 (95% CI, 0.42–0.94; p = 0.025)for the second, third, fourth, and fifth PA categories, respectively, compared with the reference category of patients with a mean PA of 0 metabolic equivalent of task-hours/week). Higher PA levels are independently associated with a lower incidence of DR in Japanese patients with type 2 diabetes.

Association between dipstick hematuria and decline in estimated glomerular filtration rate among Japanese patients with type 2 diabetes: A prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 14)]

AIMS To assess the association between dipstick hematuria and estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. METHODS Longitudinal data were obtained from 3068 Japanese patients with type 2 diabetes. To assess the independent association between dipstick hematuria and eGFR decline, we used Cox proportional hazard model adjusted for potential confounders. RESULTS Median follow-up period was 699.7days. Mean age, body mass index (BMI), and HbA1c level were 65.7years, 24.6kg/m2, and 7.5% (58.1mmol/mol), respectively. Positive dipstick hematuria was significantly associated with baseline eGFR and severity of albuminuria (p<0.001). The multivariable-adjusted hazard ratio for eGFR decline in patients with dipstick hematuria compared with those without dipstick hematuria was 2.19 [95% confidence interval (CI): 1.22-3.91]; this association remained significant even after the exclusion of patients who did not have diabetic retinopathy (hazard ratio: 2.39; 95% CI: 1.13-5.04). CONCLUSION Positive dipstick hematuria was associated with severity of albuminuria and renal function. A significant association was found between dipstick hematuria and increased risk of eGFR decline among patients with type 2 diabetes. Therefore, our results suggest that dipstick hematuria is perhaps indicative of more severe diabetic nephropathy.