Haruko Kitaoka

Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus

This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.

Acarbose improved severe postprandial hypotension in a patient with diabetes mellitus.

Postprandial hypotension (PPH) is defined as a decrease of systolic blood pressure by more than 20 mmHg after meals. Severe PPH is a troublesome diabetic complication, which has no established means of treatment. We encountered a patient who had diabetes mellitus complicated by severe PPH and attempted to treat this problem using several medications (octreotide, midodrine hydrochloride, and acarbose). A 58-year-old male with diabetic triopathy complained of orthostatic dizziness and vertigo after meals. The blood pressure was monitored for 24 h with an ambulatory blood pressure monitor, revealing that the systolic blood pressure decreased markedly after breakfast and dinner by 45 and 50 mmHg, respectively. PPH was not improved by a subcutaneous injection of octreotide. Administration of midodrine hydrochloride reduced the frequency of hypotensive episodes from twice to once daily, but the magnitude of the postprandial fall in blood pressure was still around 30 mmHg. After the patient started to receive acarbose therapy, the postprandial fall in blood pressure was diminished to 18 mmHg and his symptoms largely disappeared. For the treatment of PPH in diabetic patients, our experience suggests that it may be appropriate to try first on alpha-glucosidase inhibitor like acarbose.

Anti-Aquaporin-4 Antibody-Positive Neuromyelitis Optica Presenting with Syndrome of Inappropriate Antidiuretic Hormone Secretion as an Initial Manifestation

The distribution of neuromyelitis optica (NMO)-characteristic brain lesions corresponds to sites of high aquaporin-4 (AQP4) expression, and the brainstem and hypothalamus lesions that express high levels of AQP4 protein are relatively characteristic of NMO. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the important causes of hyponatremia and results from an abnormal production or sustained secretion of antidiuretic hormone (ADH). SIADH has been associated with many clinical states or syndromes, and the hypothalamic-neurohypophyseal system regulates the feedback control system for ADH secretion. We report the case of a 63-year-old man with NMO, whose initial manifestation was hyponatremia caused by SIADH. Retrospective analysis revealed that the serum anti-AQP4 antibody was positive, and an MRI scan showed a unilateral lesion in the hypothalamus. SIADH recovered completely with regression of the hypothalamic lesion. As such, NMO should even be considered in patients who develop SIADH and have no optic nerve or spinal cord lesions but have MRI-documented hypothalamic lesions.

Pulmonary diffusing capacity, serum angiotensin-converting enzyme activity and the angiotensin-converting enzyme gene in Japanese non-insulin-dependent diabetes mellitus patients

We investigated the independent change in pulmonary diffusing capacity (DLCO) as one manifestation of pulmonary microangiopathy and to analyze the correlation between DLCO and serum ACE. We also examined the association between DLCO and the ACE genes. We examined pulmonary functions, especially %DLCO/VA (DLCO corrected by alveolar volume, percent predicted) in 54 NIDDM patients and 34 age-matched normal control subjects. Subjects were subdivided according to the degree of retinopathy. Serum ACE level was assayed by a colorimetric method in 54 patients and an insertion/deletion polymorphism in the ACE gene was amplified using the polymerase chain reaction in 52 of the 54 patients. There was a significant reduction of %DLCO/VA (percent predicted P < 0.05) in diabetic patients. In the proliferative retinopathy (PDR) group. %DLCO/VA was significantly (P < 0.05) lower than in the no diabetic retinopathy (NDR) and simple diabetic retinopathy (SDR) groups. Although the levels of serum ACE were within normal ranges in all diabetic groups, %DLCO/VA was negatively correlated with serum ACE values (r = 0.49, P < 0.0002, y = -1.4x + 109.3). Differences among DD, ID and II type of the ACE gene, with respect to the incidence of abnormal values of each clinical parameter, were not significant. DLCO was significantly reduced in patients with PDR and the serum ACE was significantly related to impaired DLCO. Our study suggests the existence of microangiopathic involvement of pulmonary vessels in NIDDM patients.

The Relation of Urinary 8-OHdG, A Marker of Oxidative Stress to DNA, and Clinical Outcomes for Ischemic Stroke

Background: Oxidative stress/free radical generation after ischemic stroke contributes to neuronal cell injury. We evaluated the utility of an oxidative stress marker, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), to demonstrate an association between the changes of 8-OHdG and outcomes after acute ischemic stroke. Methods: We enrolled 44 patients (26 males and 18 females) who visited our hospital due to acute ischemic stroke. Urine was collected on admission and on Days 7, and 8-OHdG was measured by ELISA. The relationships between 8-OHdG levels, stroke subtypes, and clinical outcomes based on the NIHSS and modified Rankin Scale (mRS) upon discharge was evaluated. Results: In the overall cohort, the mean urinary level of 8-OHdG on Day 7 was increased than that on Day 0. The 8-OHdG levels on Day 0 were not different between patients with poor and good outcomes. However, an increasing rate from Day 0 to 7 (Δ 8-OHdG) in stroke patients with a poor outcome(mRS ≥3) was significantly higher than those with a good outcome (mRS ≤2) (2.54 vs 39.44, p = 0.004). Conclusions: The biochemical changes related to 8-OHdG and oxidative stress may be considered a marker of ischemic brain injury and clinical outcome of ischemic stroke.

Severe insulin allergy successfully treated with continuous subcutaneous insulin infusion

Insulin allergy is a rare complication of insulin therapy. Proper management, though difficult, is critical. Here, we report the case of a patient with type 2 diabetes and insulin allergy, successfully treated with continuous subcutaneous insulin infusion (CSII).

Oval pupil in patients with diabetes mellitus : examination by measurement of the dark-adapted pupillary area and pupillary light reflex

Determination of the dark-adapted pupillary area (DAPA) by infrared photography revealed that some diabetic patients show corectopia (oval pupil) in addition to the small DAPA as pupillary abnormalities. The prevalence and clinical details of oval pupil were compared between diabetic patients and healthy subjects. Pupillary light reflexes were also analyzed with an infrared videopupillography in some of the diabetic patients. The healthy subjects were examined for the influence of age on the ratio of the pupillary diameter of the major and minor axes. The ratio was 1.04 +/- 0.02 (mean +/- S.D.) in the healthy subjects, and cases in which the ratio was +2 S.D. or higher than the mean ratio were defined as oval pupil. Oval pupil was observed in 21 (24%) of 86 diabetic patients, and was correlated with heart rate variation (P < 0.05) and DAPA (P < 0.01), which represent an autonomic dysfunction. Quantitative analysis of pupillary light reflexes with an infrared videopupillography revealed that the dark-adapted pupillary area before photic stimulation (P < 0.01) and the maximum %-velocity of constriction (P < 0.05) were significantly less in the oval pupil group than in the round pupil group. Cranial magnetic resonance imaging revealed no abnormalities in the oval pupil group. From these results, a peripheral autonomic disorder was implicated in the etiology of oval pupils in diabetic patients.

A patient with diabetes mellitus, cardiomyopathy, and a mitochondrial gene mutation: confirmation of a gene mutation in cardiac muscle

A 44-year-old woman with diabetes mellitus, cardiomyopathy, and a mitochondrial gene mutation, was reported. She was diagnosed as having diabetes at 33 years of age and was treated with insulin. However, she stopped treatment 6 months later and had no medical care until she developed diabetic ketoacidosis at 41 years of age. She had diabetic foot, diabetic retinopathy, and nephropathy with low insulin secretory capacity, leading to insulin treatment. A point mutation of the mitochondrial tRNA(Leu(UUR)) gene was identified in peripheral leukocytes at 43 years of age, and sensorineural hearing impairment was detected at the same time. Her mother also suffered from diabetes mellitus with deafness and her son, who was not diabetic at age 19, had the same mitochondrial DNA (mtDNA) mutation. At 44 years of age, she developed congestive heart failure due to cardiomyopathy, and the same mtDNA mutation was identified in the cardiac muscle. Thus, it is very likely that in this patient, diabetes and cardiomyopathy was caused by the same abnormality, the point mutation of mitochondrial tRNA(Leu(UUR)) gene.

Refractory Cryptococcus neoformans Meningoencephalitis in an Immunocompetent Patient: Paradoxical Antifungal Therapy-Induced Clinical Deterioration Related to an Immune Response to Cryptococcal Organisms.

We present a case of refractory Cryptococcus neoformans meningoencephalitis in an immunocompetent woman. Her clinical symptoms did not improve with 6 months of antifungal therapy, and MRI abnormalities, indicating severe meningeal and cerebral inflammation, persisted despite a decreasing cryptococcal antigen titer. The patient continued to deteriorate despite antifungal therapy, and her condition clearly improved following treatment with adjunctive corticosteroid. We postulate that the paradoxical antifungal therapy-related clinical deterioration was due to an immune response to cryptococcal organisms, which responded to corticosteroids. These observations provide rationale for a further evaluation of corticosteroids in the management of select cases of C. neoformans central nervous system infection.

Neurologic disorders associated with anti-glutamic acid decarboxylase antibodies: A comparison of anti-GAD antibody titers and time-dependent changes between neurologic disease and type I diabetes mellitus

To determine clinical features of neurologic disorders associated with anti-glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time-dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2), cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients without neurologic disorders. Anti-GAD-Ab titers and index were higher in neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis. Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD-Ab titers and index provide clinically meaningful information about their diagnostic accuracy.