Associations of Pericardial Fat Area Determined by Routine Chest Computed Tomography With Coronary Risk Factors and Coronary Artery Disease.

BACKGROUND: Pericardial fat has been reported to be associated with coronary risk factors and severity of coronary arterial lesions. Previous studies had measured pericardial fat volume (PFV) by using contrast-enhanced cardiac computed tomography (CT) when pericardial fat was quantified. We determined pericardial fat area (PFA) in the cross section with the height of sternal angle by using routine chest CT. METHODS: We picked up 252 patients who underwent chest and abdominal CT, and we selected patients whose coronary arteries were evaluated by coronary angiography or coronary CT. Coronary artery disease (CAD) was defined as more than 75% lumen stenosis. PFA was defined as any pixel with CT attenuation of -150 to -30 Hounsfield Unit (HU) within the pericardial sac at the sternal angle level. RESULTS: Fifty-three patients were eligible. PFA was significantly larger in men than in women. Serum high-density lipoprotein (HDL)-cholesterol level was significantly and negatively correlated with PFA. Hemoglobin A1c and carotid arterial intima-media thickness tended to be positively correlated with PFA. PFA was significantly and nearly 50% larger in patients with CAD than in patients without CAD. The cut-off value of PFA was 10.4 cm2, and sensitivity and specificity of PFA for CAD were 53.8% and 88.0%, respectively. CONCLUSIONS: Present study is the first to show a significant association of PFA with gender and CAD. PFA can be determined by routine chest CT, and is simpler and more reproducible, and PFA is more available in a greater number of medical institutes as compared with PFV. Present study also showed a discriminatory value of PFA for CAD comparable to PFV.

The Influences of Withdrawal and Daily Dose Reduction of Pioglitazone on Metabolic Parameters in Patients With Type 2 Diabetes: A Retrospective Longitudinal Observational Study.

BACKGROUND: The aim of the study was to understand the influences of withdrawal or dose reduction of pioglitazone in patients with type 2 diabetes. METHODS: We retrospectively picked up patients who had undergone withdrawal or daily dose reduction of pioglitazone after a continuous prescription for 3 months or longer between January 2010 and March 2014. We compared the data before the withdrawal or dose reduction of pioglitazone with the data at 3 or 6 months after those by a chart-based analysis. RESULTS: Among 713 patients taking pioglitazone at least once during the studied period, 20 patients had undergone withdrawal of pioglitazone (group A) and 51 patients had undergone daily dose reduction (group B). The mean pioglitazone dose at baseline was 23 mg in subjects of group A, and 30 mg in group B. The number of subjects who had taken high-dose metformin (≥ 1,000 mg) and dipeptidyl peptidase-4 (DPP-4) inhibitors increased after the withdrawal or dose reduction of pioglitazone in both groups. Although no significant change was observed in plasma glucose and HbA1c levels, body weight significantly decreased at 3 and 6 months after the dose reduction in group B. The same tendency was observed in group A. Serum high-density lipoprotein-cholesterol (HDL-C) levels significantly decreased at 3 and 6 months after the withdrawal in group A. The serum alanine aminotransferase levels significantly increased 3 months after the withdrawal in group A. CONCLUSIONS: Present study demonstrated that the withdrawal of pioglitazone exacerbated serum HDL-C and liver function in patients with type 2 diabetes, although glycemic control could be maintained by using high-dose metformin or DPP-4 inhibitors.

Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Metabolic Parameters in Patients With Type 2 Diabetes: A Chart-Based Analysis.

BACKGROUND: Effects of the new class of anti-diabetic drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, on metabolic parameters in patients with type 2 diabetes remain largely unknown. METHODS: We retrospectively picked up patients who had been continuously prescribed SGLT2 inhibitors for 1 month or more between April 2014 and November 2015 by a chart-based analysis, and compared the data before the SGLT2 inhibitor treatment with the data at 1, 2, 3 and 6 months after the SGLLT2 inhibitor treatment started. RESULTS: Fifty patients were eligible for the analyses in our study. The HbA1c levels as well as body weight significantly decreased at 1, 2, 3 and 6 months after the start of SGLT2 inhibitors. Systolic blood pressure tended to decrease only at 1 and 2 months, but there was no change at 3 and 6 months. No significant change was observed in serum high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and non-HDL-C levels. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels significantly decreased at 3 and 6 months after the prescription. The hematocrit levels significantly increased at 1, 2, 3 and 6 months, and the estimated glomerular filtration rate (eGFR) levels significantly decreased at 1 month after the start of SGLT2 inhibitors. A significant correlation between reductions in HbA1c levels and HbA1c levels at baseline was observed at 1, 3 and 6 months. The decreases in serum ALT levels were also significantly correlated with the baseline ALT levels at 3 and 6 months. CONCLUSION: Present study demonstrated that SGLT2 inhibitors significantly reduced HbA1c and body weight and improved liver functions, whereas no significant change was observed in serum lipid profiles.

The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an established independent risk factor for hepatocellular carcinoma (HCC). T2DM is associated with non-alcoholic steatohepatitis (NASH), which is a major cause of non-HBV and non-HCV-related HCC; nevertheless, it has been difficult to identify those patients with T2DM who have a high risk of developing HCC. The aim of this study was to identify genetic determinants that predispose T2DM patients to HCC by genotyping T2DM susceptibility loci and PNPLA3. METHODS: We recruited 389 patients with T2DM who satisfied the following three criteria: negative for HBs-Ag and anti-HCV Ab, alcohol intake <60 g/day, and history of T2DM >10 years. These patients were divided into two groups: T2DM patients with HCC (DM-HCC, n = 59) or those without HCC (DM-non-HCC, n = 330). We genotyped 51 single-nucleotide polymorphisms (SNPs) previously reported as T2DM or NASH susceptibility loci (PNPLA3) compared between the DM-HCC and DM-non-HCC groups with regard to allele frequencies at each SNP. RESULTS: The SNP rs738409 located in PNPLA3 was the greatest risk factor associated with HCC. The frequency of the PNPLA3 G allele was significantly higher among DM-HCC individuals than DM-non-HCC individuals (OR 2.53, p = 1.05 × 10(-5)). Among individuals homozygous for the PNPLA3 G allele (n = 115), the frequency of the JAZF1 rs864745 G allele was significantly higher among DM-HCC individuals than DM-non-HCC individuals (OR 3.44, p = 0.0002). CONCLUSIONS: PNPLA3 and JAZF1 were associated with non-HBV and non-HCV-related HCC development among Japanese patients with T2DM.

Sodium-Glucose Cotransporter 2 Inhibitors: Possible Anti-Atherosclerotic Effects Beyond Glucose Lowering.

The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We searched by using Pubmed, and found 770 published articles about SGLT-2 inhibitors. Among 10 kinds of SGLT-2 inhibitors, the number of published articles about dapagliflozin was the greatest among SGLT-2 inhibitors. Since SGLT-2 inhibitors have similar chemical structures, we concentrated on the published articles about dapagliflozin. SGLT-2 inhibitors are proved to be significantly associated with weight loss and reduction of blood pressure by a relatively large number of studies. The studies investigating effects of dapagliflozin on visceral fat, insulin sensitivity, serum lipids, inflammation and adipocytokines are very limited. An influence of increase in glucagon secretion by SGLT-2 inhibitors on metabolic risk factors remains unknown.

A possible difference in the mechanism for postprandial hypoglycemia associated with dumping syndrome between patients with and without type 2 diabetes.

Dumping syndrome is a complication of gastric surgery including bariatric surgery, and which is induced by rapid gastric emptying and increased intestinal motility. We should note that hypoglycaemia due to dumping syndrome can occur in patients with type 2 diabetes. However, the pathogenesis of dumping syndrome in patients with type 2 diabetes is not fully investigated. We investigated the changes in plasma glucose, serum insulin, plasma glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) by the 75 g oral glucose tolerance test (OGTT) in 3 patients with and without type 2 diabetes who had gastric surgery. Significant hyperinsulinemia was observed in non-diabetic patients, but not in a diabetic patient. On the other hand, plasma GLP-1 levels significantly increased after glucose intake in a diabetic patient. Increased secretion of GLP-1 may have caused reactive hypoglycaemia in patients with type 2 diabetes undergoing gastric surgery.

Associations between lower extremity muscle mass and metabolic parameters related to obesity in Japanese obese patients with type 2 diabetes.

Background. Age-related loss of muscle mass (sarcopenia) increases the incidence of obesity in the elderly by reducing physical activity. This sarcopenic obesity may become self-perpetuating, increasing the risks for metabolic syndrome, disability, and mortality. We investigated the associations of two sarcopenic indices, the ratio of lower extremity muscle mass to body weight (L/W ratio) and the ratio of lower extremity muscle mass to upper extremity muscle mass (L/U ratio), with metabolic parameters related to obesity in patients with type 2 diabetes and obesity. Methods. Of 148 inpatients with type 2 diabetes treated between October 2013 and April 2014, we recruited 26 with obesity but no physical disability. Daily physical activity was measured by a triaxial accelerometer during a period of hospitalization, and which was also evaluated by our previously reported non-exercise activity thermogenesis questionnaire. We measured body composition by bioelectrical impedance and investigated the correlations of L/W and L/U ratios with body weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), visceral fat area, subcutaneous fat area, serum lipid profile, and daily physical activity. Results. The L/W ratio was significantly and negatively correlated with BMI, WC, WHR, body fat mass, body fat percentage, subcutaneous fat area, and serum free fatty acid concentration, was positively correlated with daily physical activity: the locomotive non-exercise activity thermogenesis score, but was not correlated with visceral fat area. The L/U ratio was significantly and positively correlated with serum high-density lipoprotein cholesterol. Conclusions. High L/W and L/U ratios, indicative of relatively preserved lower extremity muscle mass, were predictive of improved metabolic parameters related to obesity. Preserved muscle fitness in obesity, especially of the lower extremities, may prevent sarcopenic obesity and lower associated risks for metabolic syndrome and early mortality.

Daily Physical Activity Assessed by a Triaxial Accelerometer Is Beneficially Associated with Waist Circumference, Serum Triglycerides, and Insulin Resistance in Japanese Patients with Prediabetes or Untreated Early Type 2 Diabetes.

AIM: To investigate the association between daily physical activity and metabolic risk factors in Japanese adults with prediabetes or untreated early type 2 diabetes (T2D). METHODS: Daily physical activity level was measured using a triaxial accelerometer. We assessed correlations between physical activity level and waist circumference, blood pressure, fasting levels of plasma glucose, serum triglycerides, and insulin and homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS: A total of 80 patients were studied. After adjustment for age and body mass index, in all subjects, physical activity level was negatively associated with waist circumference (ß = -0.124, P = 0.018) and fasting serum triglycerides (ß = -0.239, P = 0.035), insulin (ß = -0.224, P = 0.022). In men, physical activity level was negatively associated with systolic blood pressure (ß = -0.351, P = 0.044), fasting plasma glucose (ß = -0.369, P = 0.025) and insulin (ß = -0.362, P = 0.012), and HOMA-IR (ß = -0.371, P = 0.011). No significant associations were found between physical activity level and metabolic risk factors in women. CONCLUSION: Objectively measured daily physical activity is beneficially associated with waist circumference, serum triglycerides, and insulin resistance in individuals with prediabetes or untreated early T2D. (This trial is registered with UMIN000015774.).

Causative anti-diabetic drugs and the underlying clinical factors for hypoglycemia in patients with diabetes.

Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association between hypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide (approximately 45%-76%) and thiazolidinediones (approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high HbA1c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.

Effects of intake of fish or fish oils on the development of diabetes.

The association between fish and fish oils intake and diabetes remains largely unknown. Here we systematically reviewed published articles (clinical trials, prospective cohort studies, systematic reviews and meta-analyses) about the effects of intake of fish or fish oils on the development of diabetes. An intake of fish oils seems not to affect insulin sensitivity, insulin secretion, beta-cell function or glucose tolerance. There is a considerable statistical heterogeneity in the overall summary estimates of the association between fish or fish oils consumption and the development of type 2 diabetes, which is partly explained by geographical differences. Marine n-3 polyunsaturated fatty acids have beneficial effects on the prevention of type 2 diabetes in Asian populations.

Effects of 6-month sitagliptin treatment on glucose and lipid metabolism, blood pressure, body weight and renal function in type 2 diabetic patients: a chart-based analysis.

BACKGROUND: Sitagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors which prevent the inactivation of incretins, increasing the endogenous active incretin levels. Incretins stimulate insulin secretion from pancreatic ß-cells and inhibit glucagon secretion from pancreatic α-cells, which is favorable for the treatment of diabetes. Sitagliptin is released on December, 2009, in Japan. We retrospectively studied effects of 6-month-treatment with sitagliptin on glucose and lipid metabolism, blood pressure, body weight and renal function in patients with type 2 diabetes by a chart-based analysis. METHODS: We retrospectively studied 220 type 2 diabetic patients who have taken sitagliptin for 6 months by a chart-based analysis. Subjects studied include patients treated with sitagliptin monotherapy, sitagliptin add-on therapy, and switching from glinide to sitagliptin. We selected patients who have both data before and after 6-month sitagliptin treatment and compared the data before the sitagliptin treatment with the data at 6 month after the sitagliptin treatment started. Body weight, blood pressure, plasma glucose, hemoglobin A1c (HbA1c), serum lipids, and estimated glomerular filtration rate in type 2 diabetic patients were measured almost at the same time points before and after 6-month-treatment with sitagliptin. RESULTS: Body weight was significantly reduced after 6-month sitagliptin treatment by 0.8 kg. HbA1c levels were also significantly decreased after the sitagliptin treatment by 0.6%. We found a significant and negative correlation between change in body weight and body mass index at baseline. We also observed a significant and negative correlation between change in HbA1c and HbA1c levels at baseline. The number of patients who showed the absence of urinary glucose was significantly increased after the sitagliptin treatment.

Elevated pancreatic enzymes, IgM, soluble interleukin-2 receptor in anti-GADab(+) type 1 diabetes.

Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.