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Aims/Introduction The present study aimed to analyze the temporal changes in the prevalence, screening rate, visual impairments and treatment patterns of diabetic retinopathy in the Korean population over 8 years. Materials and Methods This was a retrospective population-based study of Korean national health insurance beneficiaries aged 30 years or older with type 2 diabetes, obtained from the Korean National Health Insurance Claims database from 2006 to 2013 ( n = 1,655,495 in 2006 and 2,720,777 in 2013). The annual prevalence rates of diabetes, diabetic retinopathy, dilated fundus examinations, visual impairment, laser treatment and vitrectomy, as determined based on diagnostic and treatment codes, were analyzed. Results There was a steady increase in the prevalence of diabetic retinopathy, from 14.3% in 2006 to 15.9% in 2013. However, the incidence of new diabetic retinopathy cases decreased from 6.7/100 person-years in 2006 to 5.6 in 2013. Approximately 98% of patients underwent at least one dilated fundus examination during the follow-up period. The prevalence of diabetic retinopathy peaked in the 60-69 years age group. The prevalence of diabetic retinopathy was higher in female than in male diabetes patients. The proportion of patients who underwent an annual dilated fundus examination improved from 24.3% in 2006 to 30.0% in 2013. Among patients with diabetic retinopathy, constant decreases in the proportions of those who received laser treatment (11.4% in 2006 to 6.9% in 2013) and who underwent vitrectomy (2.4% in 2006 to 1.7% in 2013) were noted. Additionally, a decreasing trend in the prevalence of visual impairment was noted among the patients with diabetic retinopathy, from 2% (4,820/237,267) in 2006 to 0.08% (3,572/431,964) in 2013. Conclusions Although there was a rapid increase in the prevalence of diabetes in the Korean population in the past decade, the prevalence of diabetic retinopathy remained stable during the study period. However, just three out of 10 patients with diabetes underwent regular annual dilated fundus examinations. Thus, an improvement in the continuity of diabetic retinopathy screening among patients with diabetes is necessary to reduce the risk of visual impairment as a result of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Based on our previous observations that clusterin induction accompanies pancreas regeneration in the rat, we sought to determine if regeneration might be impaired in mice that lacked clusterin. We studied the impact of absent clusterin on morphogenic and functional features of regenerating pancreas. Clusterin induction was accompanied in the regenerating pancreas by a robust development of new lobules with ductules, acini, and endocrine islets in wild type after partial pancreatectomy. In clusterin knock-out mice, however, pancreatectomy resulted in a poor formation of regenerating lobule. In particular, regeneration of beta-cells was also significantly reduced and was associated with persistent hyperglycemia. Duct cells obtained from pancreatectomized clusterin knock-out mice exhibited impaired beta-cell formation in vitro; this was restored by administration of exogenous clusterin. We suggest that clusterin plays a critical role to promote both exocrine and endocrine regeneration following pancreas injury, as well as for in vitro beta-cell regeneration. Developmental Dynamics 240:605-615, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Leptin and insulin are important anorexigenic hormones acting on the hypothalamus. However, most obese humans and animals have reduced hypothalamic responses to leptin and insulin. Increased endoplasmic reticulum (ER) stress has been shown to cause insulin resistance in the livers of obese animals. In the present study, we investigated a role of ER stress in the development of central leptin and insulin resistance. Intracerebroventricular (ICV) administration of the ER stress inducer thapsigargin (TG) increased food intake and body weight. Furthermore, ICV or intra-hypothalamic administration of TG inhibited the anorexigenic and weight-reducing effects of leptin and insulin. ICV administration of TG by itself activated signal-transduction-activated-transcript-3 (STAT3) and Akt in the hypothalamus, but prevented a further activation of hypothalamic STAT3 and Akt by leptin and insulin. We also found that the expression of the ER stress markers such as phosphorylation of the inositol-requiring kinase-1 (IRE1), spliced form of X-box-binding protein-1 (XBP-1s), glucose-regulated/binding immunoglobulin protein-78, and C/EBP homology protein (CHOP) increased in the hypothalami of diet-induced obese (DIO) mice. Furthermore, treatment of chemical chaperone 4-phenyl butylic acid significantly improved central leptin resistance in DIO mice. These findings suggest that increased hypothalamic ER stress in obese animals may induce central leptin and insulin resistance. [ABSTRACT FROM AUTHOR]

Background Although elevated serum concentrations of γ-glutamyltrans- ferase (GGT) or alanine aminotransferase (ALT) have been associated with type 2 diabetes mellitus, it is unclear whether each is an independent predictor of type 2 diabetes or merely a surrogate marker for fatty liver or hepatic injury. Methods We assessed clinical and laboratory findings in 3556 non-diabetic subjects (2217 men, 1339 women; age, 45.7 ± 8.1 (range 20-79) years) without fatty liver or clinically significant hepatic dysfunction who underwent voluntary medical check-ups at a 5-year interval. Results The odds ratio of developing type 2 diabetes increased significantly with increasing GGT and ALT levels at baseline. In multiple logistic regression models adjusted for age, sex, alcohol consumption, smoking, body mass index (BMI), triglycerides, high-density lipoprotein (HDL)-cholesterol, fasting glucose, and ALT, the highest quartile of GGT remained significantly associated with type 2 diabetes. Compared with the first GGT quartile, the odds ratios of the second, third, and fourth GGT quartiles were 0.64 (95% CI, 0.25-1.65), 1.12 (0.45-2.78), and 3.07 (1.21-7.76), respectively. The adjusted odds ratios for the second, third, and fourth ALT quartiles in the same logistic regression model were 2.40 (0.83-6.94), 2.85 (1.03-7.90), and 4.31 (1.56-11.88), respectively. The risk of type 2 diabetes was additive with respect to GGT and ALT quartiles. Conclusions Increased serum GGT and ALT levels are independent, additive risk factors for the development of type 2 diabetes mellitus in subjects without fatty liver or hepatic dysfunction. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Mitochondrial transcription factor A (Tfam, previously mtTFA) is a key regulator of mitochondrial DNA (mtDNA) transcription and replication. We have reported that overexpression of nuclear respiratory factor-1 (NRF-1) and high concentration (50 mM) of glucose increased the promoter activity of the rat Tfam in L6 rat skeletal muscle cells. In this study, we investigated the mechanism of high glucose-induced Tfam transactivation. The addition of 50 mM glucose for 24 h increased Tfam promoter activity up to twofold. The glucose-induced Tfam expression was dose-dependent and cell-type specific. Glucose increased the Tfam promoter-driven transactivity in L6 (skeletal muscle), HIT (pancreatic beta-cell), and CHO (ovary) cells, but not in HepG2 (hepatoma), HeLa, and CV1 (kidney) cells. Among various monosaccharides, only glucose and fructose increased the Tfam promoter activity. Oxidative stress might not be involved in glucose-induced Tfam expression since treatment with antioxidants such as vitamin C, vitamin E, probucol, or α-lipoic acid did not suppress the induction. None of the inhibitors of protein kinase C, MAP kinase, and PI3 kinase altered the glucose-induced Tfam promoter activity, suggesting that general phosphorylation is involved in its signaling. However, a dominant negative mutant of NRF-1, in which 200 amino acids of C-terminus were truncated, completely suppressed the glucose-induced Tfam induction. It was concluded that high glucose-induced Tfam transcription in L6 cells might be mediated by NRF-1. [ABSTRACT FROM AUTHOR]

OBJECTIVES Increased urinary albumin excretion (UAE) in diabetic and nondiabetic subjects is frequently associated with insulin resistance syndrome and central obesity. Cushing's syndrome is also characterized by central obesity and insulin resistance. This study was undertaken to see whether increased UAE is found in Cushing's syndrome. DESIGN Cross-sectional study. PATIENTS Thirteen consecutive patients with Cushing's syndrome. MEASUREMENTS Patients collected three overnight urine samples for the measurement of UAE by radioimmunoassay. UAE was also measured in 479 nondiabetic subjects who comprised the control population for this study. In the patients who had initial microalbuminuria, UAE was remeasured 2 months after successful removal of pituitary or adrenal tumours. Kidney biopsy was performed in three patients during adrenalectomy. RESULTS Eleven out of 13 patients (84.6%) had increased UAE (> 9.6 μg/min), and eight patients (61.5%) had microalbuminuria or overt proteinuria (> 20 μg/min). Kidney biopsy revealed apparently normal glomerular structures without evidence of diabetic nephropathy. After correction of hypercortisolaemia, UAE declined profoundly in all of the patients. CONCLUSIONS More than 80% of patients with Cushing's syndrome had increased UAE. This was almost completely reversed after successful treatment of hypercortisolaemia. These results indicate that endogenous hypercortisolaemia increases UAE by a mechanism that is presently unknown. [ABSTRACT FROM AUTHOR]

OBJECTIVE Previous studies have demonstrated that endogenous insulin secretion is not suppressed by exogenous insulin in patients with insulinoma. In this study we examined whether insulin secretion in insulinoma patients is suppressed by exogenous insulin during hypoglycaemia. SUBJECTS AND METHODS Sixteen insulinoma patients (5 men and 11 women) and 10 normal subjects were studied. Hyperinsulinaemic glucose clamp studies were performed at both euglycaemia (4.5 mmol/l glucose) and hypoglycaemia (2.5 mmol/l glucose). RESULTS In normal subjects, plasma C-peptide levels were suppressed by 66% during the euglycaemic hyperinsulinaemic clamps (P < 0.01). In contrast, in insulinoma patients, plasma C-peptide levels increased by 25% during the clamps (P < 0.05). In the hypoglycaemic hyperinsulinaemic clamps, plasma C-peptide levels were nearly completely (91%) suppressed in normal subjects and partially (39%) suppressed in patients with insulinoma (P < 0.01). The decrease in C-peptide levels during the hypoglycaemic clamps was > 30% in 12 (75%) of 16 insulinoma patients and > 50% in 8 (50%) patients. CONCLUSIONS This study demonstrated that in patients with insulinoma, insulin secretion was not suppressed by exogenous insulin during euglycaemia but was suppressed during hypoglycaemia, although the degree of suppression was less than that in normal subjects. Our results suggest that the feedback regulation of insulin secretion by exogenous insulin is partially retained in patients with insulinoma. [ABSTRACT FROM AUTHOR]

Carcinoid tumors derived from neuroendocrine cells can release serotonin and other vasoactive substances into the systemic circulation, resulting in carcinoid syndrome. Testicular carcinoid, a rare disease accounting for less than 1% of all testicular neoplasms, rarely manifests symptoms of carcinoid syndrome. We describe a case of carcinoid syndrome arising from a primary testicular carcinoid tumor. A 21-year-old male patient presented with facial flushing and diarrhea for 5 years. He had an enlarged left testis and a 1-cm, ill-defined, hard, non-tender mass in his right testis. His 24 h urinary excretion of 5-hydroxyindoleacetic acid was elevated (16.1 mg/day). Somatostatin receptor scintigraphy correlated with carcinoid tumor in both testes. Following bilateral orchiectomy, the patient's facial flushing and diarrhea disappeared. [ABSTRACT FROM AUTHOR]

Background: Although elevated serum concentrations of gamma-glutamyltrans- ferase (GGT) or alanine aminotransferase (ALT) have been associated with type 2 diabetes mellitus, it is unclear whether each is an independent predictor of type 2 diabetes or merely a surrogate marker for fatty liver or hepatic injury., Methods: We assessed clinical and laboratory findings in 3556 non-diabetic subjects (2217 men, 1339 women; age, 45.7 +/- 8.1 (range 20-79) years) without fatty liver or clinically significant hepatic dysfunction who underwent voluntary medical check-ups at a 5-year interval., Results: The odds ratio of developing type 2 diabetes increased significantly with increasing GGT and ALT levels at baseline. In multiple logistic regression models adjusted for age, sex, alcohol consumption, smoking, body mass index (BMI), triglycerides, high-density lipoprotein (HDL)-cholesterol, fasting glucose, and ALT, the highest quartile of GGT remained significantly associated with type 2 diabetes. Compared with the first GGT quartile, the odds ratios of the second, third, and fourth GGT quartiles were 0.64 (95% CI, 0.25-1.65), 1.12 (0.45-2.78), and 3.07 (1.21-7.76), respectively. The adjusted odds ratios for the second, third, and fourth ALT quartiles in the same logistic regression model were 2.40 (0.83-6.94), 2.85 (1.03-7.90), and 4.31 (1.56-11.88), respectively. The risk of type 2 diabetes was additive with respect to GGT and ALT quartiles., Conclusions: Increased serum GGT and ALT levels are independent, additive risk factors for the development of type 2 diabetes mellitus in subjects without fatty liver or hepatic dysfunction., (Copyright 2009 John Wiley & Sons, Ltd.)