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Endocrinology AND Hyperlipidemia [keywords]
- Colestimide improves glycemic control via hepatic glucose production in db/db mice. [JOURNAL ARTICLE]
- Endocr J 2014 Feb 19.
The objective of this study was to assess the chronic effects of a bile acid sequestrant, colestimide, on glucose metabolism. After db/db mice were fed a diet containing colestimide or cholic acid (CA) for 12 weeks, we investigated the impact of these agents on glucose and lipid metabolism. Colestimide significantly reduced the elevated fasting blood glucose level (p<0.01), and CA even more markedly reduced fasting blood glucose. The blood glucose level after an oral glucose load was significantly lower in the CA group than in the control group, but the colestimide group showed no significant difference. The insulin response to a glucose load was abolished in the control and colestimide groups. A hyperinsulinemic-euglycemic clamp study revealed that colestimide significantly improved the GIR (p=0.013). Hepatic EGP and Rd were also improved by colestimide, suggesting that it alleviated insulin resistance by suppressing hepatic glucose production and increasing peripheral glucose usage. CA significantly increased both the weight and cholesterol content of the liver, while colestimide reduced these parameters. Colestimide suppressed SHP expression, but enhanced SREBP2 expression. On the other hand, CA increased the expression of SHP and lipogenic enzymes such as ACC and SCD-1, but had no effect on SREBP2. The present study demonstrated that colestimide improves hyperglycemia and hyperlipidemia, as well as reducing the hepatic lipid content. In contrast, CA exacerbates hyperlipidemia and increases the hepatic lipid content, although it improves glycemic control. Thus, colestimide is a well-balanced drug for the treatment of diabetes mellitus.
- Diabetes mellitus and the risk of Alzheimer's disease: a nationwide population-based study. [Journal Article, Research Support, Non-U.S. Gov't]
- PLoS One 2014; 9(1):e87095.
Possible association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence.Data were collected from Taiwan's National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74 ± 14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD.Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p<0.001). After Cox proportional hazard regression model analysis, DM (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.50-2.07, p<0.001), age (HR, 1.11; 95% CI, 1.10-1.12, p<0.001), female gender (HR, 1.24; 95% CI, 1.06-1.46, p=0.008), hypertension (HR, 1.30; 95% CI, 1.07-1.59, p=0.01), previous stroke history (HR, 1.79; 95% CI, 1.28-2.50, p<0.001), and urbanization status (metropolis, HR, 1.32; 95% CI, 1.07-1.63, p=0.009) were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD (HR, 2.17; 95% CI, 1.04-4.52, p=0.039).Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk.
- Can group medical clinics improve lipid management in diabetes? [Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, Non-P.H.S.]
- Am J Med 2014 Feb; 127(2):145-51.
Group medical clinics may improve diabetes and hypertension control, but data about dyslipidemia are limited. We examined the impact of group medical clinics on lipids among patients with uncontrolled diabetes and hypertension.Prespecified secondary analysis of 239 veterans randomized to group medical clinics or usual care. Lipids were assessed at study baseline, midpoint, and end. We used linear mixed models to compare lipid levels between arms and generalized estimating equation models to compare low-density lipoprotein cholesterol (LDL-C) goal attainment. An additional post hoc analysis examined intensification of cholesterol-lowering medications in both arms.At baseline, mean total cholesterol was 169.7 mg/dL (SD 47.8), LDL-C 98.2 mg/dL (SD 41.7), and high-density lipoprotein cholesterol (HDL-C) 39.3 mg/dL (SD 13.0). Median baseline triglycerides were 131 mg/dL (interquartile range 122). By study end, mean total cholesterol and LDL-C in group medical clinics were 14.2 mg/dL (P = .01) and 9.2 mg/dL (P = .02) lower than usual care, respectively; 76% of group medical clinic patients met goals for LDL-C, versus 61% of usual care patients (P = .02). Triglycerides and HDL-C remained similar between study arms. Treatment intensification occurred in 52% of group medical clinic patients, versus 37% of usual care patients between study baseline and end (P = .04). The mean statin dose was higher in group medical clinic patients at study midpoint and end.Group medical clinics appear to enhance lipid management among patients with diabetes and hypertension. This may be a result of greater intensification of cholesterol-lowering medications in group medical clinics relative to usual care.
- Vitamin D concentrations in familial combined hyperlipidemia: effects of lipid lowering treatment. [Journal Article]
- Diabetol Metab Syndr 2014; 6(1):7.
Vitamin D deficiency has been linked to several cardiovascular risk factors but information regarding vitamin D concentrations in familial combined hyperlipidemia (FCHL) is lacking. Our objective was to examine vitamin D concentrations in patients with FCHL and to study the effects of lipid-lowering therapy.We conducted a cross sectional study on 59 patients with FCHL and 48 healthy controls. We analyzed 25-hydroxyvitamin D (25(OH)D) concentrations and their association with lipid parameters, anthropometric measures, C-reactive protein and homeostasis model assessment (HOMA) index. Twenty-three patients with FCHL were also included in a longitudinal study conducted to analyze 25-hydroxyvitamin D concentrations before and after treatment for dyslipidemia.After adjustment for body mass index and seasonality, patients with FCHL had lower vitamin D concentrations than controls. Adjusted means (standard error of the mean (S.E.M)) for 25(OH)D according to the presence or absence of FCHL were 62.8 (3.6) nmol/L for patients with FCHL and 74.8 (4.1) nmol/L for controls (p = 0.021). In FCHL, hypovitaminosis D was associated with features of atherogenic dyslipidemia. After lipid-lowering therapy, vitamin D concentrations increased (51.0 ± 31.3 to 58.9 ± 24.6 nmol/L (P = 0.022)). However, changes in 25(OH)D concentrations did not correlate with changes in other parameters.Our findings suggest that FCHL is associated with decreased vitamin D concentrations and that treatment for dyslipidemia improves vitamin D status through an unknown mechanism. Further studies are needed to replicate these data in larger populations and to elucidate the mechanisms involved in this association.
- Maternal diabetes or hypertension and lifestyle factors may be associated with metabolic syndrome: a population-based study in Taiwan. [Journal Article, Research Support, Non-U.S. Gov't]
- Kaohsiung J Med Sci 2014 Feb; 30(2):86-93.
Early detection and interventions for metabolic syndrome (MetS) are the most cost-effective methods for preventing many chronic diseases. There have been discordant findings in various countries due to different genetics and lifestyles. The goal of this study was to investigate the association of MetS with parental diseases, a Chinese-style diet, and rural-urban regional differences with a large-scale epidemiological survey in Taiwan. Data were obtained from the Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), a cross-sectional population-based study with multistage stratified random sampling conducted by the Taiwan Bureau of Health Promotion in 2002. Public health nurses visited homes to conduct the survey, including blood drawing and an interview. Multiple logistic regression analysis was used for exploring the factors associated with MetS. A total of 6591 people completed data for analysis. Our results revealed that older age, male sex, and maternal diabetes or hypertension, were significantly associated with MetS. Eating poultry with skin and fat and eating a bean-free diet may be associated with a higher risk of MetS. People who exercised regularly and the residents of the Taipei metropolitan area had a lower prevalence of MetS. As a result, people with maternal diabetes or hypertension should pay attention to their cardiovascular health and prevention of MetS. We suggest that eating skinless and low-fat poultry, eating more beans, and exercising regularly, may decrease the risk of MetS. We should make an effort to advocate for health promotion, including lifestyle modification, especially among the high-risk population and among residents in rural areas with limited medical resources.
- Potential anti-atherosclerotic effects of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus. [Journal Article]
- Curr Diab Rep 2014 Feb; 14(2):463.
Cardiovascular disease (CVD) is the leading cause of mortality in patients with diabetes. Pharmacotherapy that can reduce hyperglycemia and also exhibit pleiotropic effects that can result in a reduction in cardiovascular disease will be a major advance. Recently, the dipeptidyl-peptidase-4 inhibitors were introduced as ant-hyperglycemic therapy. Studies from numerous groups have reported effects that could potentially result in a reduction in CVD. Some of the drugs in this class, especially vildagliptin and sitagliptin, have been shown to reduce postprandial hyperlipidemia following a fat load, improve endothelial function as evidenced by increased forearm blood flow, and also display anti-inflammatory effects. Their effects on platelet function, blood pressure, and oxidative stress are very preliminary and need to be confirmed. Finally, they have been shown to reduce subclinical atherosclerosis by reducing carotid intimal-medial thickness. However, the final arbiter with respect to a reduction in CVD will be the ongoing clinical trials.
- Endocrinological and cardiological late effects among survivors of childhood acute lymphoblastic leukemia. [Journal Article]
- Turk J Haematol 2013 Sep; 30(3):290-9.
Objective:Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and
Methods:Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders) and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions.
Results:Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%), with 8 of them (21%) having multiple problems. Six (16%) of the survivors were obese and 8 (21%) of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21%) subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21%) patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction.
Conclusion:We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least one adverse event occurred in most of our cases. Conflict of interest:None declared.
- Dyslipidemia, kidney disease, and cardiovascular disease in diabetic patients. [Journal Article, Research Support, Non-U.S. Gov't]
- Rev Diabet Stud 2013 Summer-Fall; 10(2-3):88-100.
This article reviews the relationship between dyslipidemia, chronic kidney disease, and cardiovascular diseases in patients with diabetes. Diabetes mellitus is associated with complications in the cardiovascular and renal system, and is increasing in prevalence worldwide. Modification of the multifactorial risk factors, in particular dyslipidemia, has been suggested to reduce the rates of diabetes-related complications. Dyslipidemia in diabetes is a condition that includes hypertriglyceridemia, low high-density lipoprotein levels, and increased small and dense low-density lipoprotein particles. This condition is associated with higher cardiovascular risk and mortality in diabetic patients. Current treatment guidelines focus on lowering the low-density lipoprotein cholesterol level; multiple trials have confirmed the cardiovascular benefits of treatment with statins. Chronic kidney disease also contributes to dyslipidemia, and dyslipidemia in turn is related to the occurrence and progression of diabetic nephropathy. Different patterns of dyslipidemia are associated with different stages of diabetic nephropathy. Some trials have shown that treatment with statins not only decreased the risk of cardiovascular events, but also delayed the progression of diabetic nephropathy. However, studies using statins as the sole treatment of hyperlipidemia in patients on dialysis have not shown benefits with respect to cardiovascular risk. Diabetic patients with nephropathy have a higher risk of cardiovascular events than those without nephropathy. The degree of albuminuria and the reduction in estimated glomerular filtration rate are also correlated with the risk of cardiovascular events. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to reduce albuminuria in diabetic patients has been shown to decrease the risk of cardiovascular morbidity and mortality.