We studied the effect of pioglitazone on obese type 2 diabetic patients with fatty liver. Pioglitazone was associated with reduced HbA₁c and improved liver function in such patients and was not associated with any weight increase. BMI was significantly higher in those with improved liver function than in those with worsened or unchanged liver function. A 66-year-old woman diagnosed with type 2 diabetes mellitus and nonalcoholic fatty liver disease and treated with pioglitazone showed improved HbA₁c and liver function with no weight increase. We found in needle biopsy that the number of fatty cells in the liver decreased over a 6-month period, compared to the number of fatty cells observed prior to treatment. Our results suggest that pioglitazone is an effective oral hypoglycemic agents in treating diabetes mellitus and nonalcoholic fatty liver disease.

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To clarify insulin treatment in the elderly, we compared twice-daily insulin injection regimens in type 2 diabetic patients in four age groups. Daily insulin doses in groups were not changed, but older patients tended to consume more insulin in the morning and less insulin in the evening than middle-aged diabetics, i.e., the ratio of insulin doses in the morning to daily insulin doses increased but decreased in the evening among the elderly. We found no relationship of these ratios to renal function. An age-related decrease in urinary CPR excretion was observed, but plasma CPR levels before and after breakfast did not differ among groups. Daily plasma insulin profiles in patients with twice-daily injections of premixed insulin consisting of 30% aspart and 70% protaminated insulin aspart were higher in the elderly than in the middle-aged. Delayed insulin metabolism thus may affect insulin injection regimens in elderly patients. These results show that aging is an important factor in determining insulin regimens.

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Diabetic subjects numbering 133 were divided into 3 groups—smokers, exsmokers, and nonsmokers—and their degree of depression compared based on Problem Areas in Diabetes (PAID). PAID and Zung Self-Reporting Depression Scale scores did not differ significantly among groups, but fewer of smokers than ex-and nonsmokers exercised regularly. We also studied changes in emotional status after patients stopped smoking, finding that 50% of the smokers taking part in a smoking cessation program continued to abstain from smoking and to exercise, improving their PAID scores from 43 points to 31 points. Regular exercise appears to enhance such individuals' ability to stop smoking, and this ability may in turn decrease diabetes-related distress levels.

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Patients with diabetes mellitus (DM) suffer from complications such as micro-and macroangiopathy, yet few epidemiological reports have considered other complications. We studied disease frequency and susceptibility in patients with and without DM. Using a discharge summary, we counted the number of diseases in patients aged 40 years and above based on patient ID to avoid overlap. This data was classified into DM and non-DM groups. From January 1,1998, to March 31,2004, 2,884 DM patients were seen with 21,280 diseases and 21,480 non-DM patients seen with 71,740 diseases. By disease, we compared the percentage of patients having complications (frequency) between DM and non-DM groups. Disease susceptibility was calculated by the frequency of DM patients divided by that of non-DM patients. Frequency of and susceptibility to (parentheses) selected diseases among DM patients was as follows: tuberculosis, 1.8% (1.7); hepatoma, 5.7% (2.2); hypertensive disease, 45.4% (3.2); acute myocardial infarction, 6.0% (3.4); ischemic heart disease, 35.0% (4.3); cerebral infarction, 21.5% (3.1); pneumonia, 8.3% (1.4); and renal failure, 14.1% (3.8). This analysis, which considers all diseases in patients, effective provides a comprehensive view of complications in patients with diabetes.

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To determine the epidemiological status of diabetic polyneuropathy (DPN) and the usefulness of Achilles tendon reflex (ATR) in clinical DPN diagnosis, we clinically surveyed DPN in patients with diabetes mellitus, working with 448 clinics and hospitals in Tohoku, northeastern Japan. The survey consisted of questionnaires on subjective DPN symptoms and ATR examination and vibration perception.
Data came from 14,744 patients with diabetes mellitus aged 64.2±11.9 years [mean±SD], with a diabetes duration of 9.7±7.7 years, and HbA₁c 7.4±2.5%. The frequency of DPN symptoms was 18.8%, the absence or decrease in ATR 40.3%, and the decrease in vibration perception threshold 52.0%. The frequency of DPN was 27.6% based on the general decision of the physician in charge and 35.8% based on simplified diagnostic criteria of the Japanese Study Group on Diabetic Neuropathy, consisting of subjective symptoms of DPN, a decrease in ATR, and decreased threshold of vibration perception. ATR disappeared earlier than the appearance of subjective symptoms of DPN after diabetes onset. The frequency of loss of ATR was significantly higher in patients with subjective symptoms of DPN than in those without symptoms.
These results indicate a high frequency of DPN and the significance and usefulness of ATR, a simple and easy examination, in diagnosing DPN.

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A 35-year-old man having ulcerative colitis for about 6 years and fulminant type 1 diabetes mellitus was seized with severe thirst and nausea on November 23, 2006, and realized that his diarrhea had increased from about 10 times a day to over than 30. He was seen on December 1. Laboratory findings on admission were plasma glucose of 1,172 mg/dl (65.1 mmol/l), HbA₁c of 6.1%, elevated serum pancreas enzymes, and a large amount of urine ketone bodies. Tests for evaluating his endogenous insulin secretion showed markedly decreased insulin secretion. He was diagnosed with diabetic ketoacidosis and started on insulin.
Although many patients with fulminant type 1 diabetes mellitus report abdominal symptoms, we know of no case having simultaneous ulcerative colitis. We discuss the association between these diseases in pathogenesis.

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[in Japanese]

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A 81-year-old woman admitted for memory disturbance and type 2 diabetes mellitus was obese and hypertensive. Serum HbA₁c was 8.7% and HOMA-R 5.08. Her standard score of mini mental state examination (MMSE) was 24 and 21 in Hasegawa's dementia scale-revised (HDS-R). She showed serious impairment in delayed recall, orientation, and executive function, and was diagnosed with probable Alzheimer's disease (AD) based on diagnostic criteria of the National Institute of Neurological and Communicative Disorders and Strokes-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). She was treated with metformin and glimepiride for diabetes and donepezil for AD, but her brain function declined to 19 in MMSE and 17 in HDS-R after 18 months. We added pioglitazone, and after 5 months, her HbA₁c fell to 6.3% and her HOMA-R to 2.89. Her brain dysfunction improved in several cognitive domains including short-term memory. Her MMSE score recovered to 24 and her HDS-R to 21, and she showed several improvements in daily performance. Pioglitazone thus appears to partially restore the cognitive AD decline in elderly diabetic patients.

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Objective: We clarified HLA distribution and diabetic microangiopathy in fulminant type 1 diabetes, a novel subtype of diabetes mellitus.
Methods: We identified patients with fulminant type 1 diabetes in Japan by using criteria established in 2004. In Study 1, HLA analysis, we studied the serotype of HLA A, DR, and DQ in 115 patients with fulminant type 1 diabetes, 98 patients with autoimmune (type 1A) diabetes, and 190 healthy controls. In Study 2 on diabetic microangiopathy, we studied clinical parameters including blood glucose, HbA₁c, and serum C peptide levels, the frequency of severe hypoglycemia, optic fundus, urinary albumin excretion, and Achilles tendon reflex in 41 patients with fulminant type 1 diabetes and 76 patients with autoimmune (type 1A) diabetes as controls.
Results: Study 1 showed that HLA DR4, DQ4, and DR4-DQ4 haplotype were significantly more frequent in patients with fulminant type 1 diabetes than in healthy control subjects. The homozygosity of HLA DR4-DQ4 indicated a very high odds ratio of 13.3. HLA DR1, DR2, DR5, DR8, DQ1, haplotypes of DR2-DQ1 and DR8-DQ1 were significantly less frequent in patients with fulminant type 1 diabetes. Study 2 showed that the 5-year cumulative incidence of microangiopathy was 24.4% in fulminant type 1 diabetes and 2.6% in type 1A diabetes. In longitudinal studies, the cumulative incidence of each form of microangiopathy was significantly higher in fulminant type 1 diabetes than in type 1A diabetes; retinopathy was 9.8% vs 0%, nephropathy 12.2% vs 2.6%, and neuropathy 12.2% vs 1.3%. Mean HbA₁c levels were similar in fulminant and type 1A diabetes groups during follow-up, but mean M and the frequency of severe hypoglycemic episodes were significantly higher and mean postprandial C-peptide level significantly lower in the fulminant type 1 diabetes group.
Conclusions: Our results suggest that (1) class II HLA contributes to the development of fulminant type 1 diabetes, and (2) patients with fulminant type 1 diabetes belong to a subgroup at high risk for diabetic microangiopathy.

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