[in Japanese]

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This study have investigated the clinical status of subjects with type 2 diabetes mellitus starting dipeptidyl peptidase-4 inhibitors (DPP4i) and examined the efficacy of multiple oral hypoglycemic agents (OHA) with DPP-4i as add-on therapy. Subjects treated with DPP-4i as add-on therapy accounted for 61.5 % of 1,656 patients that started with DPP-4i and completed follow-up for six months. The percentages of the patients treated with one, two or three OHAs agents combined with DPP-4i were 31, 50 and 18 %, respectively. A three-drug combination, i.e. sulfonylureas, biguanides and DPP-4i was the most frequently used pattern of multiple drugs with DPP-4i and accounted for 35 % of all multiple regimen. The mean HbA1c improved significantly from 7.75±1.00 % to 6.96±0.92 % after 6 months of DPP-4i combined with OHA treatment. The reduction in the HbA1c level over 6 months did not show a significant difference in the groups with different numbers of OHAs (1-3) with DPP-4i and in the patterns of multiple therapy. These findings suggested that the addition of DPP-4i to multiple OHAs was effective for primary diabetes care.

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The aim of this study was to clarify the relationship between treatment satisfaction and dropout rates. We conducted an outpatient questionnaire and examined the relationship between treatment satisfaction evaluated by the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and intension to drop out. The DTSQ score was significantly lower in the patients who had the intension to drop out compared with those who did not (21.6±6.9 vs. 26.2±6.2, P=0.006). Receiver operating characteristic analysis revealed that the DTSQ score could predict intension to drop out (area under the curve 0.696, P=0.006), and the best cutoff value was 22.5 (63.2 % sensitivity and 70.8 % specificity). These results indicate a significant correlation between treatment satisfaction and intension to drop out. An attempt to increase treatment satisfaction may be an important strategy to reduce the intension to drop out and possibly the dropout rate.

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A 32-year-old man presented in a coma {GCS (E1, V2, M2) } due to hypoglycemic encephalopathy. Diffusion-weighted MRI (DWI) , performed immediately after the patient lapsed into a coma, demonstrated high-intensity signal areas in the bilateral subcortex, including the corona radiata and caudate nucleus. While these signals, observed on MRI, transiently increased on day 3, they had decreased by day 7. On day 20, he showed recovery of consciousness, and the signals, observed on DWI, had completely disappeared by day 20. Three months later, he was discharged after activities of daily living, such as walking and conversation, had greatly improved. Herein, we present this diabetic patient with hypoglycemic encephalopathy, showing sequential DWI findings, i.e. the restricted high-intensity signal areas in the bilateral subcortex and their extinctions, to be very useful for predicting the functional outcomes of patients with severe hypoglycemia.

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A 45-year-old woman had suffered from dry cough, thirst and polyuria for 10 days before admission. She was diagnosed as having fulminant type 1 diabetes mellitus based on her HbA1c level (NGSP, 6.9 %), plasma glucose level, (27 mmol/l, 488 mg/dl), fasting serum C-peptide (0.2 ng/ml), and the presence of ketonuria. C-peptide levels were under the detectable range during a glucagon tolerance test. It was not typical that not only Glutamic Acid Decarboxylase (GAD) Antibody but also Insulinoma-associated Antigen-2 (IA-2) Antibody were detected, and that the serum lipase level had only moderately increased (55 IU/l [normal range 0-49]). The serotypes of HLA were DR4 and DQ4 (DR4-DQ4 haplotype). She also had systemic scleroderma. We report very few cases of fulminant type 1 diabetes mellitus with double positive GAD and IA-2 antibodies.

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The patient was a 91-year-old male who was diagnosed with type 2 diabetes at 60 years of age, and started insulin treatment at 78 years of age. His HbA1c was 10.6 % (NGSP value) at the first visit to the hospital, despite the administration of 61 units of insulin. An abdominal examination revealed elastic-hard masses at the insulin injection sites in his abdomen. The patient was admitted for further examination. T1- and T2-weighted MRI images showed low intensity masses with no signal inhibition on fat-suppressed images. His skin biopsy samples were pale with an eosinophilic nonstructural substance stained orange with Congo-Red. The lesions were thus diagnosed as insulin injection-induced local amyloid deposition. The required insulin dose was markedly decreased after changing the insulin injection sites. In addition, the blood insulin levels were markedly lower when insulin was injected into the amyloid-deposited region than into healthy skin, thus indicating markedly reduced insulin absorption from the region containing amyloid. The first case of reduced insulin absorption due to insulin injection-induced local amyloid deposition reported as a possible cause of poor blood glucose control.

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A 92-year-old woman with senile dementia in a nursing home presented to the emergency department with tachypnea following loss of appetite that had lasted for two days. Diabetes mellitus had never been diagnosed. Urinalysis revealed ketonuria, and a serum glucose level of 986 mg/dl. Arterial blood gas analysis revealed anion gap metabolic acidosis. The patient was diagnosed as having diabetic ketoacidosis and insulin therapy was initiated, which proved effective. Other laboratory testing revealed a lack of insulin secretion, negative findings for islet-related autoantibodies, and a low hemoglobin A1c level of 6.4 %. These finding fulfill the diagnostic criteria of fulminant type 1 diabetes mellitus. A search of the literature in Japan showed that she was the oldest patient who had developed type 1 diabetes mellitus, including the non-fulminant subtypes. Physicians should remember that elderly patients with dementia, as in our case, might not exhibit the typical diabetic symptoms in the onset of fulminant type 1 diabetes mellitus.

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This report presents a case of emphysematous cystitis that was difficult to distinguish from a gastrointestinal perforation in an 82-year-old male diabetic patient. This patient was diagnosed as having type 2 diabetes when he came to the hospital for the treatment of a left transcervical fracture. He developed a slight fever of 37 °C and anorexia in the beginning of July, and these symptoms did not improve with over the counter drugs (OTC). He went to the Emergency Room (ER) of this hospital on July 17, because of recurrent vomiting. Abdominal CT revealed excessive accumulation of gas in the small intestine. He was hyperglycemic and had increased plasma CRP. Therefore, he was diagnosed to have a ileus and was hospitalized. The hypogastric pain increased the next day, and abdominal CT showed free gas in the pelvic cavity. Therefore, exploratory laparotomy was performed with a preoperative diagnosis of gastrointestinal perforation. No gastrointestinal perforation was found during surgery, but snow-ball crepitation and edematous change were observed in the bladder wall. A cystoscope test showed submucosal accumulation of bubbles and he was diagnosed to have emphysematous cystitis. Treatment including urethral catheterization, antibiotics and insulin for glycemic control upon fasting resolved the inflammation as well as the images of gas in the bladder wall.

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A 48-year-old male had previously been diagnosed with Charcot-Marie-Tooth (CMT) disease. He had developed thirst, polyuria and polydipsia at age of 45, and was hospitalized for poorly controlled diabetes (HbA1c 10.8 % (NGSP) ) at age of 46. He had visceral obesity (body weight 84.0 kg, BMI 28.1 kg/m² and waist circumference 101 cm) and muscle atrophy of the distal extremities at the time of admission. A hyperinsulinemic-euglycemic clamp study showed severe insulin resistance in the peripheral tissues (metabolic clearance rate (MCR) 4.38 ml/kg/min). A liver biopsy sample revealed nonalcoholic fatty liver disease (NAFLD) with hepatic steatosis and fibrosis (NAFLD class 2, steatosis 2, grade 0.5, stage 2). He started bolus insulin therapy together with diet and exercise therapy. He successfully lost 19.6 kg (body weight 64.4 kg, BMI 21.8 kg/m² and waist circumference 75.5 cm) and obtaining good glycemic control with HbA1c about 5 % after 1.5 years. His insulin resistance had markedly improved (MCR 6.86 ml/kg/min), and the liver steatosis and fibrosis had disappeared (NAFLD class 0, steatosis 0, grade 0, stage 0). Lifestyle intervention may therefore be useful for achieving an improvement of insulin resistance and glycemic control in obese diabetic patients with CMT disease.

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A 77-year-old male with hypertension was admitted to the hospital because of hypoglycemia. He had a history of back pain, and Loxoprofen had been prescribed for 1 month. The level of immunoreactive insulin was 196.6 μU/ml, anti-insulin antibody was positive, and HLA typing indicated the presence of the DRB1^*04: 06 allele. The patient had not taken any medications, except for Loxoprofen, amlodipine, candesartan and hydrochlorothiazide. Therefore, he was diagnosed to have insulin autoimmune syndrome (IAS). He was initially permitted to take small meals 5 times a day to avoid hypoglycemia; however, hypoglycemia was observed several times. Subsequently, the patient was treated with an α-glucosidase inhibitor to decrease the frequency of hypoglycemia. Continuous glucose monitoring (CGM) showed that the α-glucosidase inhibitor could prevent hypoglycemia due to IAS. In conclusion, an α-glucosidase inhibitor should be considered for the treatment of hypoglycemia due to IAS. Further, CGM is useful for monitoring hypoglycemia.

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We have revised a part of the diagnostic criteria for fulminant type 1 diabetes as "Criteria for definite diagnosis of fulminant type 1 diabetes mellitus (2012)". The new criteria were set both to express the essence of this disease associated with a rapid increase of the patients' blood glucose and to be highly sensitive to reduce the misdiagnosis. After analyzing the data of 382 patients with newly-diagnosed fulminant type 1 diabetes, we adopted a HbA1c level of 8.7 % (NGSP value) as the cut-off value. The new criterion had 100 % sensitivity and the best value by the ROC (receiver operation curve) analysis.
In addition, we added a comment that "This value (HbA1c <8.7 % in NGSP) is not applicable for patients with previously diagnosed glucose intolerance" to the new criteria, and also a comment that "An association with HLA DRB1^*04: 05-DQB1^*04: 01 has been reported" as a related finding.
We did not revise the screening criteria or the other parts of the diagnostic criteria, because they are still reliable.

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