Ipragliflozin Improves Hepatic Steatosis in Obese Mice and Liver Dysfunction in Type 2 Diabetic Patients Irrespective of Body Weight Reduction.

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis.

One-minute mental status examination for category fluency is more useful than mini-mental state examination to evaluate the reliability of insulin self-injection in elderly diabetic patients.

AIMS/INTRODUCTION: We investigated the factors associated with the reliability of insulin self-injection in elderly diabetic patients receiving insulin therapy. MATERIALS AND METHODS: We enrolled diabetic patients aged ≥65 years and receiving insulin therapy, and assessed their cognitive function by the mini-mental state examination and 1-min mental status examination for category fluency. We also observed their technique of insulin self-injection, and evaluated whether or not patients were able to inject insulin by themselves according to nine defined details in terms of insulin self-injection. The predictive factors for the reliability of insulin self-injection were determined by univariate and multivariate logistic regression analysis. There were 278 participants (135 males, 143 females) enrolled in the present study. RESULTS: According to multivariate logistic regression analysis, only the 1-min mental status examination score was found to be a significant independent predictor of the reliability of insulin self-injection (odds ratio 0.75; 95% confidence interval 0.62-0.90; P = 0.002). CONCLUSIONS: The 1-min mental status examination for category fluency can be considered more useful than mini-mental state examination to evaluate the reliability of insulin self-injection in elderly diabetic patients receiving insulin therapy.

[A questionnaire survey on current status of anti-diabetic therapy for diabetic patients with dementia].

AIM: It is important to establish treatment goals and optimal anti-diabetic therapy for diabetic patients with dementia. However, there are currently no established treatment guidelines. Recently, the West Tokyo Diabetes Association has established the Diabetes and Dementia Study Group to investigate the status of anti-diabetic therapy for diabetic patients with dementia. Here, we assessed the current status of such patients by a questionnaire survey. METHODS: In November 2011, we conducted a mailed survey to the clinics and hospitals affiliated with Kita-Tama, Hachioji and Tachikawa Medical Associations in Tokyo, Japan. The survey evaluated the most suitable anti-diabetic therapy for elderly diabetic patients or diabetic patients with dementia, combined anti-diabetic therapy, insulin therapy for elderly diabetic patients and diabetic patients with dementia, combination therapy of insulin and oral anti-diabetic agents for diabetic patients with dementia, factors that make it difficult for diabetic patients with dementia to continue insulin therapy, and selection of treatment or care for diabetic patients with dementia. RESULTS: The responses indicated that the anti-diabetic agents appropriate for diabetic patients with dementia are dipeptidyl peptidase-4 inhibitors. Those inappropriate for the same patients are metformin and insulin. Family support was a major factor for insulin therapy continuation for diabetic patients with dementia. Moreover, anti-diabetic agents for these patients are selected according to their ease of use and compatibility with available familial and social resources. CONCLUSION: Our survey results can be utilized for the creation of new guidelines and educational resources for the anti-diabetic therapy of diabetic patients with dementia.

[Endosaccular embolization of an intrasellar aneurysm with hypopituitarism: case report].

An 81-year-old male presented with weight loss and hyponatremia. A baseline endocrinological examination revealed anterior pituitary dysfunction. A computed tomography and MRI revealed a large, unruptured intrasellar aneurysm protruding from the right internal carotid artery and pushing the pituitary stalk leftward. The patient developed polyuria and polydipsia from 10 days after commencing corticosteroid supplementation and was diagnosed with partial central diabetes insipidus (DI). Balloon assisted endosaccular embolization was performed about one month after the posterior pituitary dysfunction was identified. The unruptured aneurysm was successfully embolized with Guglielmi detachable coils (GDCs) without narrowing of the parent vessel. DI resolved completely and the posterior pituitary dysfunction improved soon after endosaccular embolization. The remission of DI after coil embolization suggested that the DI might have been induced by the progressive mass effect of the aneurysm rather than by the steroid. An endocrinological evaluation and cerebral angiography confirmed partial recovery of anterior pituitary dysfunction and almost complete obliteration of the aneurysm, respectively at 1 year after the operation. We report a case of hypopituitarism secondary to the large intrasellar aneurysm. This aneurysm was embolized with GDCs, resulting in partial recovery of anterior pituitary dysfunction and complete recovery of posterior pituitary dysfunction.

A case with primary aldosteronism due to unilateral multiple adrenocortical micronodules.

A 46-year-old male with long-term treatment-resistant hypertension and past history of cerebral hemorrhage was found to have suppressed plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) with aldosterone/renin ratio of 25.3. Furosemide plus upright test did not stimulate PRA, but computed tomography scan of the abdomen revealed no abnormal lesions in either adrenal gland. Selective adrenal venous sampling (SAVS) showed that PAC in the left and the right adrenal vein were 1000 ng/dl and 230 ng/dl, respectively, which increased to 1500 ng/dl and 620 ng/dl, respectively, after ACTH stimulation. Diagnosis of primary aldosteronism due to hypersecretion of aldosterone from the left adrenal gland was made, and laparoscopic left adrenalectomy was performed. Pathological examination of the 'apparently normal' adrenal tissue resected revealed the presence of poorly encapsulated multiple adrenocortical micronodules which showed positive immunoreactivity for 3beta-hydroxysteroid dehydrogenase by immunohistochemical study, but negative immunoreactivity in the hyperplastic zona glomerulosa consistent with paradoxical hyperplasia associated with primary aldosteronism. Postoperatively, PRA was normalized and his high blood pressure was well controlled with lower doses of antihypertensive drugs than those used before surgery. The clinicopathological features of our case are consistent with the diagnosis of unilateral multiple adrenocortical micronodules (UMN), a new subset of primary aldosteronism, in which SAVS proved to be a useful diagnostic tool for its localization.

Olfactory neuroblastoma causing ectopic ACTH syndrome.

A 39-year-old woman who presented with typical Cushingoid appearance (moon facies, central obesity, purpura) was admitted to our hospital because of pulmonary infection. She was found to have hypertension, severe hypokalemia, and metabolic alkalosis. Endocrine data revealed elevated plasma levels of ACTH and cortisol with lack of circadian rhythm, non-suppressibility to high-dose dexamethasone, and hyperresponsiveness to CRH stimulation. Although no pituitary mass was detected by MRI of the brain, inferior petrosal sinus sampling showed a step-up of central to peripheral ACTH levels; these data are consistent with the diagnosis of Cushing's disease. She was successfully treated with metyrapone to control hypercortisolemia. Ten months later, a mass was detected in the ethmoid sinus, which was surgically removed. After resection of the ethmoid sinus tumor, her Cushingoid features and hypercortisolemia disappeared, but recurred after enlargement of a second mass in the maxillary sinus. After resection of the maxillary sinus tumor, her hypercortisolemia subsided. Histologically, the tumor tissues from both the ethmoid and maxillary sinus were identical and consistent with the diagnosis of olfactory neuroblastoma. Immunohistochemically, the immunoreactivities of ACTH and POMC were positive in the cytoplasm of tumor cells, and immunoreactive ACTH was demonstrated in both tumor tissues. Thus, this is the second rare case with ectopic ACTH syndrome caused by olfactory neuroblastoma thus far reported.

Psychosocial predictors of relapse among diabetes patients: a 2-year follow-up after inpatient diabetes education.

In a 2-year follow-up study of diabetes patients (N=309) who received 2 weeks of inpatient diabetes education, the authors investigate the relationship of several demographic, clinical, and psychosocial factors with relapse, defined as the worsening of glycemic control. The patients with no improvement in glycemic control after diabetes education were more likely to have higher scores on the depression subscale of the Profile of Mood States, compared to the patients with improvement. Kaplan-Meier survival analyses showed that patients who had no prior diabetes education, whose meals were prepared by their spouses, and who had less social support were more likely to relapse and relapsed within a significantly shorter period of time than those who had prior diabetes education, cooked for themselves, and had more social support.