[in Japanese]

View full abstract

The aim of this study was to evaluate the influence of withdrawing pioglitazone (Pio) on glycemic control and identify indicators of deterioration of the HbA1c level following Pio withdrawal in 159 type 2 diabetes subjects. The HbA1c levels were retrospectively evaluated 12 months after withdrawal. There were no restrictions on changes in other antidiabetic drugs, the use of which increased in 140 patients (88.1 %) during the observation period. Consequently, the HbA1c levels were found to be elevated by more than 1.5 % following the withdrawal of Pio in 43 patients (27.0 %) at 5.81±2.91 months on average, a rate that was significantly higher than that observed in the control group (27.0 % vs 6.9 %, p<0.000005). Furthermore, in the logistic regression analysis, a female sex and the use of three or more oral antidiabetic drugs were selected as explanatory variables for deterioration of the HbA1c level following the withdrawal of Pio. Our results indicated a marked increase in HbA1c in approximately 30 % of the subjects who discontinued Pio, with an interval of approximately six months for deterioration. We therefore suggest that withdrawing Pio therapy is likely to result in unfavorable effects on glycemic control, especially in female patients receiving multidrug therapy.

View full abstract

Objectives: Few reports have provided evidence enabling the estimation of associations between diabetes, peripheral arterial disease and the total serum bilirubin concentration. Methods: We enrolled 1,013 diabetic patients in this study and categorized them into three groups according to the ankle brachial index (ABI): ABI≤0.90 (low ABI group), 0.91-1.00 (low-normal ABI group) and≥1.01 (normal ABI group). Results: The percentage of patients in each ABI group was 5.7 %, 7.8 % and 86.5 %, respectively. Compared with the normal ABI group (≥1.01), the low ABI group (≤0.90) exhibited a significantly higher prevalence of cardiovascular disease, diabetic retinopathy and dyslipidemia, an older age, a longer history of diabetes and lower serum total bilirubin and estimated glomerular filtration rate (eGFR) values. The results showed that a low serum total bilirubin level (≤0.5 mg/dl) was associated with a 1.79-fold increase in the frequency of a low or low-normal ABI, after adjusting for age, gender, BMI, duration of diabetes and the presence of diabetic retinopathy and cardiovascular disease. Conclusions: A reduced serum total bilirubin level is associated with peripheral arterial disease. Our results suggest that a low serum total bilirubin level may therefore be used as a predictive biomarker of peripheral arterial disease.

View full abstract

We experienced a case of type 1 diabetes mellitus with concurrent distal renal tubular acidosis (dRTA) complicated by diabetic ketoacidosis (DKA). The patient was a 50-year-old man who had been diagnosed with dRTA at 9 years of age and subsequently received treatment, although diabetes mellitus was not detected at that time. In September 2013, he developed thirst, polyuria and weight loss, with a random blood glucose level of 421 mg/dl, positive urine ketone bodies (3+), HbA1c level of 11.9 % and positive anti-IA-2 and auto-insulin antibodies. An arterial blood gas analysis indicated a pH of 7.228 and a HCO₃^- level of 9.1 mmol/l. Based on these findings, he was diagnosed with DKA. On the initial visit, he had both increased anion gap (AG) metabolic acidosis and normal AG metabolic acidosis. After treating the DKA, the onset of hyperchloremic metabolic acidosis caused by dRTA became evident. Renal potassium loss and an acid excretion disorder, both caused by renal tubular dysfunction, were thereafter also observed, and particular attention to the course of treatment of DKA was therefore required. Cases of type 1 diabetes mellitus diagnosed based on the occurrence of DKA accompanied by concurrent dRTA are extremely rare. We herein report the present case while also discussing the pertinent literature.

View full abstract

A 52-year-old woman reported occasionally feeling very hungry and irritable, although the symptoms disappeared after eating. One day, she lost consciousness early in the morning; at that time, her plasma glucose (PG) level was 41 mg/dl. On admission, the patient's fasting PG level, serum insulin level and response to a 75-g oral glucose tolerance test were normal. However, her basal level of plasma proinsulin was remarkably high. She was subsequently diagnosed with insulinoma due to the high proinsulin level, the occurrence of a hypoglycemic attack after a 16-h fast and the presence of a hypervascular tumor localized in the tail of the pancreas, as evidenced on enhanced abdominal computed tomography and arterial stimulation venous sampling examinations. Following tumor resection, her symptoms disappeared. While 50 % of insulinomas from which the secretion of proinsulin is dominant relative to insulin are reported to be malignant, this case involved no malignant histological findings. Clinically, the patient has exhibited no recurrence in the last four years. This case is the fourth case of a proinsulin-dominant type insulinoma in Japan and involved the highest proinsulin/insulin levels. In cases of normal insulin secretion in patients with suspected insulinoma, it is important to rule out the possibility of over secretion of proinsulin in place of insulin.

View full abstract

We herein review the case of a 71-year-old woman who was diagnosed with diabetes mellitus due to a plasma glucose level of 500 ml/dl at 59 years of age and was started on medication. At 61 years of age, she began to receive insulin therapy. At that time, her C-peptide level in the urine was 5 μg/day and her HbA1c level was around 8-9 %. At 70 years of age, she complained of weakness of the left upper and lower limbs, staggering while walking and dysarthria. A T1 high-intensity signal region was found in the basal ganglia on head MRI. The patient's abnormal MRI findings and weakness in the upper and lower limbs disappeared following treatment of the hyperglycemia. However, the symptoms of staggering while walking and dysarthria did not improve. In addition, the titers of serum and cerebrospinal fluid anti-GAD antibodies were 37,000 U/ml and 1,700 U/ml, respectively. Recently, we found several reports of cerebellar ataxia associated with a high titer of anti-GAD antibodies; many of the patients also had diabetes mellitus. We therefore speculate that this case may have been caused by the effects of anti-GAD antibodies. Many reported patients with cerebellar ataxia and a high titer of anti-GAD antibodies also showed hyperglycemia, suggesting that there may be a relationship between cerebellar ataxia with a high anti-GAD antibody titer and hyperglycemia.

View full abstract

A 63-year-old man was admitted to a hospital in April 2012 with a disturbance of consciousness and subsequently diagnosed as being in a hypoglycemic coma based on his low plasma glucose (PG) level. He consequently recovered after receiving an intravenous infusion of glucose and was admitted to our hospital for a further examination of the hypoglycemia. On admission, the patient's fasting PG level was low (43 mg/dl), whereas the immunoreactive insulin (IRI) level was slightly high; the IRI/PG ratio was not above 0.3. A 75 gOGTT showed impaired glucose tolerance, and the plasma proinsulin level was markedly high (70.7 pmol/l). In addition, abdominal CT disclosed a hypervascular tumor in the tail of the pancreas, and a selective arterial calcium injection test was therefore performed. Consequently, a marked rise in the IRI level was observed when calcium was infused into the splenic artery, suggesting that the tumor was an insulinoma, and distal pancreatectomy was subsequently performed. After the surgery, the fasting PG level remained elevated (89 mg/dl), while the plasma proinsulin level markedly decreased (6.3 pmol/l). These observations suggest that the patient's hypoglycemia was principally caused by hyperproinsulinemia due to insulin secretion from the insulinoma.

View full abstract