We report a case of a 69-year-old man with treatment-resistant diabetic chorea presenting psychiatric symptoms. The right chorea lasted for 3 months and was refractory to control of diabetes mellitus or administration of haloperidol and benzodiazepines. Only administration of tiapride was efficacious. Magnetic resonance spectrometry and dopamine transporter-single photon emission computed tomography suggested that sustained ischemia at the striatum may lead to impaired expression of dopamine transporters, thereby resulting in deterioration in the indirect pathway. Tiapride inhibited dopamine D2 receptors, thereby restoring the function of the indirect pathway and resulting in improvement of diabetic chorea.

AIMS:Citrin is an aspartate/glutamate carrier that composes the malate-aspartate reduced nicotinamide adenine dinucleotide (NADH) shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD) and adult-onset type II citrullinemia (CTLN2). Hepatic glycolysis is essentially impaired in citrin deficiency and a low-carbohydrate diet was recommended. The lethal effect of infusion of glycerol- and fructose-containing osmotic agents was reported in these patients. Hyperalimentation was also reported to exacerbate CTLN2; however, glucose toxicity was unclear in citrin deficiency.METHODS:We studied two CTLN2 patients complicated with type 2 diabetes mellitus (DM), Case 1 presented with hyperammonemic encephalopathy accompanied with DM, while Case 2 presented with hyperammonemic encephalopathy relapse upon the onset of DM after several years' remission following supplementation with medium-chain triglycerides (MCT) and adherence to a low-carbohydrate diet.RESULTS:Insulin therapy with MCT supplementation and a low-carbohydrate diet improved hyperammonemia and liver function in Case 1. Additional insulin therapy improved hyperammonemia in Case 2.CONCLUSION:Glucose is not toxic for citrin deficiency in normoglycemia because glucose uptake and metabolism by hepatocytes are limited in normoglycemia. However, glucose becomes toxic during persistent hyperglycemia and antidiabetic therapy is indispensable for CTLN2 patients with DM.

Aim We compared the efficacy and safety of insulin degludec/insulin aspart co-formulation (IDegAsp) twice-daily to a free combination of basal insulin degludec and GLP-1 receptor agonist liraglutide (IDeg + Lira) once-daily for patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs. Subjects and Methods Eligible patients were randomly allocated at a 1:1 ratio to receive either the once-daily dual injection of IDeg + Lira (n = 24) or twice-daily single injection of IDegAsp (n = 28). The primary endpoints were as follows: HbA1c changes over 52 weeks of treatment and the percentage of participants achieving HbA1c < 7.0% at week 52. Results After 52 weeks, HbA1c decreased by 0.3% in the IDegAsp group and by 0.7% in the IDeg + Lira group. The HbA1c reduction was greater in the IDeg + Lira group than in the IDegAsp group. 19% of patients on IDegAsp versus 40% on IDeg + Lira achieved HbA1c < 7.0%. Pre-breakfast and pre-dinner blood glucose at 52 weeks were significantly lower in the IDeg + Lira group than in the IDegAsp group. The reduction in body mass index (BMI) was greater in the IDeg + Lira group than in the IDegAsp group throughout the study period. The confirmed hypoglycaemia rates were 1.32 and 0.69 per patient/year of exposure to IDegAsp and IDeg + Lira, respectively. Conclusions In patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs, treatment with the once-daily dual injection of IDeg + Lira compared with the twice-daily single injection of IDegAsp showed no significant difference in glycaemic control but statistically superior weight loss.

ABSTRACTObjective: Acromegaly is associated with metabolic and neoplastic complications, but successful treatment of acromegaly can sometimes result in growth hormone deficiency (GHD). Nonalcoholic fatty liver disease may develop in GHD, although there are few reports of such cases after cured acromegaly.Methods: We report the case of a 41-year-old woman with nonalcoholic steatohepatitis associated with GHD after surgical cure of acromegaly.Results: Growth hormone (GH) replacement therapy improved serum triglyceride, hyaluronic acid, and type IV collagen levels as well as liver function and quality of life. Computed tomography (CT) showed reduced volumes of both visceral and subcutaneous fat and an increased liver/spleen CT attenuation value.Conclusion: Cured acromegalic patients should be carefully examined if GHD and associated metabolic disorders arise. Appropriate diagnosis of GHD and prompt treatment with GH replacement should ameliorate liver dysfunction and the metabolic changes associated with GHD.Abbreviations: ALT = alanine aminotransferase AST = aspartate aminotransferase BMI = body mass index CT = computed tomography GH = growth hormone GHD = growth hormone deficiency HbA1c = glycated hemoglobin IGF-1 = insulin-like growth factor 1 NAFLD = nonalcoholic fatty liver disease NASH = nonalcoholic steatohepatitis OGTT = oral glucose tolerance test rhGH = recombinant human GH

1) Abstract The aim of this study was to determine the time course and mechanism of hypoxia‑induced pancreatic islet dysfunction. Islets isolated from Sprague Dawley rats were cultured in 1% O2 (hypoxia) . Glucose stimulated insulin secretion (GSIS) was then examined for islets in either static or perifused cultures followed by an evaluation of mitochondrial activity and islet cell death. Additionally we examined the eff ect of culturing previously hypoxic islets for an additional 24 h under normoxia to determine whether the hypoxic eff ects were reversible and to assess the eff ects of re‑oxygenation on GSIS. In the static islet culture insulin secretion declined signifi cantly after 24 h. In perifused islets the area under the curve (AUC) of fi rst‑phase GSIS declined signifi cantly after 6 h while the AUC of second‑phase GSIS decreased signifi cantly after 12 h. Mitochondrial activity dropped markedly after 48 h but cell death assays revealed that apoptosis did not increase in the time period from 6 h to 48 h. However necrosis increased signifi cantly after 24 h. In the re‑oxygenation study the return to normoxia signifi cantly worsened the decline in GSIS. In conclusion exposure to hypoxia fi rst causes functional disorder in the islets followed by cell death due to necrosis rather than apoptosis. Furthermore re‑oxygenation aggravated islet dysfunction.

Growth hormone (GH) deficiency is transient in most cases of adrenocorticotropin (ACTH) deficiency, while deficiency of both selective ACTH and GH in adults, as in the present case, is rare among hypopituitarism cases. In this patient, one year after hydrocortisone replacement for ACTH deficiency, data on GH secretion by insulin tolerance test and GH-releasing peptide-2 injection showed a partial improvement, but still there was lack of an adequate response. We consider that the patient had the deficiency of both selective GH and ACTH. Therefore, careful monitoring of GH function after the glucocorticoid replacement is required in cases of ACTH deficiency.

Serum cystatin C (CysC) has been proposed as a potentially superior marker for the evaluation of renal function because it was more sensitive and accurate for the estimation of glomerular filtration rate (GFR) than other markers. We evaluated the clinical usefulness of CysC in diabetic nephropathy. The study was performed on 414 Japanese diabetic patients. We compared serum CysC levels with serum creatinine levels, urinary concentrations of albumin, transferrin and type IV collagen, and creatinine clearance (Ccr). Then, the correlation between serum CysC levels and high-sensitivity C-reactive protein (H-CRP) levels were examined. When the patients were classified by renal function, 19% of the patients were free from nephropathy, 49% had microalbuminuria, 28% had persistent proteinuria, and 4% had end stage renal disease. The serum CysC levels increased with the progression of nephropathy, and significantly higher in overt nephropathy, but not significant in early nephropathy. Serum CysC levels were well-correlated with H-CRP levels in the patients without nephropathy. These results indicate that serum CysC would be practical for the evaluation of renal function in diabetic patients with overt nephropathy but not early nephropathy and might be related with a risk for cardiovascular events in patients without nephropathy.