Low serum bilirubin concentration is a novel risk factor for the development of albuminuria in patients with type 2 diabetes

Objective

Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes.

Materials and Methods

We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria.

Results

During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93).

Conclusions

Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.     

Elevated fasting serum insulin level predicts future development of hypertension

Background

Studies have investigated clinical association between fasting insulin level and hypertension. However, it is still debatable whether elevated fasting insulin actually increases the risk of hypertension with the passage of time. Thus, this study was aimed at investigating the association between baseline fasting insulin level and the development of hypertension.

Methods

25,062 normotensive, non-diabetic Korean men participating in a medical health check-up program were followed up from 2005 until 2010. They were divided into 4 groups according to baseline fasting insulin levels (first quartile–fourth quartile). The incidence of hypertension was compared among 4 groups, and Cox proportional hazards model was used to determine if hypertension was associated with higher baseline fasting insulin level.

Results

The incidence of hypertension increased according to the baseline fasting insulin level (first quartile: 13.3%, second quartile: 15.4%, third quartile: 17.5%, fourth quartile: 23.2%, P < 0.001). Even after adjusting for multiple covariates, the HRs (95% CI) for hypertension were higher for the second (1.12; 0.96–1.31), third (1.39; 1.20–1.62) and fourth quartile group (1.75; 1.51–2.03), compared to the first quartile group, respectively (P for trend < 0.001).

Conclusion

The risk of hypertension was in proportion to the baseline fasting insulin level. In addition, hyperinsulinemia was an independent risk factor for the future development of hypertension. These findings suggest the value of fasting insulin level as an early predictor of hypertension.     

Circulating irisin,omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk

Objective

Muscle and fat are now recognized as metabolism-regulating endocrine organs. However, muscle and adipocyte-derived novel cytokines such as irisin and omentin-1 remain understudied in relation to metabolic biomarkers that are associated with cardiovascular risk.

Subjects and methods

Thirty-nine subjects with mean (± SD) BMI of 29.2 ± 5.4 kg/m² and either diabetes or two other cardiovascular risk factors were enrolled in a 6-month randomized trial of low-dose ethanol. We examined cross-sectional data at baseline, 3-month, and 6-month visits to assess (1) within-person stability of novel cytokines (irisin, omentin-1, visfatin, resistin, and soluble tumor necrosis factor receptor II) and (2) their associations with metabolic parameters, particularly lipoprotein subparticle profile.

Results

Repeated measures of irisin and omentin-1 were highly correlated, with intra-class correlations of 0.84 (95% CI: 0.74, 0.91; P < 0.001) and 0.81 (0.70, 0.89; P < 0.001), respectively. Irisin was negatively correlated with omentin-1 (7.4% irisin decrease per a 1-SD increment in omentin-1; 95% CI: 0.5%, 13.9%; P = 0.04). In models adjusted for age, sex, and race, irisin was negatively associated with HDL cholesterol (7.3% decrease per a 10 mg/dL increment; 1.0%, 13.3%; P = 0.02) and large HDL particles (15.5% decrease per a 1-SD or 3.5-μmol/L increment; 5.2%, 24.7%; P = 0.005). Omentin-1 was positively associated with mean VLDL size (3.8% increase per a 1-SD increment; 0.06%, 7.8%; P = 0.05). Adjustment for alcohol intervention, BMI, and other cytokines did not materially affect these associations.

Conclusions

Irisin and omentin-1 are stable within-person, inversely associated with each other, and closely related to lipoprotein profile. These molecules may be promising markers for cardiovascular risk.     

The Effect of α-Cyclodextrin on postprandial lipid and glycemic responses to a fat-containing meal

Objective

α-Cyclodextrin (α-CD), a soluble dietary fiber derived from corn, marketed under the trade name FBCx®, has the potential to help individuals manage their weight and improve their lipid profiles. Initial studies in healthy overweight and/or obese diabetic individuals found that, in those consuming a normal to high fat diet over a 4 or 12 week period, α-CD use was associated with weight loss or maintenance and a reduction in triglyceride (TG) and cholesterol levels in hyperlipidemic individuals. Furthermore, α-CD use was associated with the positive effects of increasing insulin and leptin sensitivities. To date, the immediate post-prandial glucose and lipid responses to a fat-containing meal have not been reported.

Materials/Method

This double blinded placebo controlled cross-over trial examined the effect of 2 g of α-CD taken immediately following consumption of a commercially prepared high-fat breakfast meal on the acute postprandial responses in healthy adults.

Results

The coincidental consumption of α-CD with a fat-containing meal was associated with a significant reduction in postprandial TG responses over time when compared to placebo. When incremental area under the curve was calculated, the area under the curve associated with α-CD consumption was significantly smaller than the Placebo area (0.30 ± 1.07 mmol/L/3 h vs. 0.98 ± 0.88 mmol/L/3 h, p < 0.05). There were no significant changes in glucose or cholesterol levels.

Conclusion

α-Cyclodextrin was shown to significantly lower acute postprandial blood triglyceride levels.     

Fish oil supplementation alters circulating eicosanoid concentrations in young healthy men

Objective

Increasing omega-3 fatty acid (FA) intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with numerous health benefits; however, the benefits on inflammation appear to vary depending on the study population examined. While improvements in inflammatory status have been reported in the elderly, there is less evidence regarding the effects of fish oil supplementation on inflammation in young adults. The goal of the present study was to examine the influence of fish oil supplementation on lipid metabolites and the inflammatory status of young healthy men.

Materials/Methods

Fasted serum samples were collected from 10 young healthy males (23.4 ± 1.7 years) before and after a 3-month supplementation of fish-oil containing 2.0 g EPA and 1.0 g DHA. Samples were analyzed to investigate changes in FA profiles, bioclinical parameters (e.g. triglyceride and hs-CRP), and a panel of 26 eicosanoids. Paired t-tests were used to evaluate changes between the time points.

Results

Serum triglycerides decreased (P = 0.0006) while the proportion of HDL-c (relative to total cholesterol) increased significantly (P = 0.0495) after fish oil supplementation. Specific monounsaturated and polyunsaturated FA levels were changed following supplementation, including reductions in palmitoleic and oleic acid, and, as expected, increases in EPA and DHA. We also observed increases in eicosanoids, namely prostaglandin-F2α (P < 0.0001) and thromboxane-B2 (P = 0.0296), after fish oil supplementation.

Conclusions

A 3-month fish oil supplementation in young healthy men improved circulating triglyceride levels and the HDL-c ratio while, concomitantly, increasing the concentrations of two eicosanoids (prostaglandin-F2α and thromboxane-B2). This suggests that fish oil supplementation does have significant benefits in young healthy adults and that specific omega-6-derived eicosanoids can help to further our understanding regarding the beneficial link between omega-3 FA and inflammation.     

Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics

Aim

To investigate severe hypoglycaemia (SH) in adults with type 1 diabetes and its associations with impaired awareness of hypoglycaemia (IAH), clinical, psychological and socio-demographic factors.

Methods

Attendees of three specialist diabetes clinics in Melbourne, Australia completed questions about frequency of SH in the past six months; impaired awareness of hypoglycaemia (Gold score); and measures of general emotional well-being (WHO-5), diabetes-specific positive well-being (subscale of W-BQ28), diabetes-related distress (PAID) and fear of hypoglycaemia (HFS).

Results

Of 422 participants (mean ± SD age 37.5 ± 15.0 years; 54% women), 78 (18.5%) reported at least one SH event and 86 (20.5%) had IAH. SH and IAH frequencies were similar at all clinics. In total, 194 SH events were reported, with 10 people experiencing 40% of events. Compared with those without SH, participants with SH had longer diabetes duration, were younger at diabetes onset and more likely to have IAH (p < 0.01). Those with SH had greater fear of hypoglycaemia and diabetes-related distress, poorer general emotional well-being, and lower diabetes-specific positive well-being, (p < 0.01). There were no associations with age, gender, insulin regimen or HbA1c.

Conclusions

This study has identified that SH and IAH in Australian adults with type 1 diabetes exist at similar levels to those reported in US and European research. SH was significantly associated with IAH and fear of hypoglycaemia.Assessment of hypoglycaemia, IAH and psychological well-being as part of a routine diabetes clinic visit was well accepted by attendees and enabled identification of those who may benefit from medical, educational or therapeutic interventions.     

Effects of a single bout of aerobic exercise on short-term low-carbohydrate/high-fat intake-induced postprandial glucose metabolism during an oral glucose tolerance test

Objective

A single bout of exercise can improve acute postprandial glucose metabolism aggravated by short-term low-carbohydrate/high-fat diet (HFD). The purpose of this study was to investigate the effect of a single bout of aerobic exercise on short-term HFD-induced postprandial glucose and incretin metabolism during an oral glucose tolerance test (OGTT).

Materials/Methods

Eleven healthy young men (age [mean ± SE] 27 ± 1 years; body mass index, 22 ± 1 kg/m²) performed three, 3-day interventions in randomized order: (1) a normal diet (ND: ~ 22% fat), (2) an HFD (~ 69% fat) and (3) an HFD with a single bout of aerobic exercise (HFDEx). The exercise (50% peak oxygen consumption; ~ 200 kcal) was performed on the third day in HFDEx. An OGTT was performed after each 3-day dietary intervention.

Results

The incremental area under the curve (iAUC) of plasma glucose levels during the OGTT was significantly higher in the HFD and HFDEx trials than in the ND trial (P = 0.001). In addition, the iAUC of glucagon-like peptide-1 (GLP-1) level was significantly higher in the HFD trial than in the ND and HFDEx trials (P = 0.04). The first-phase insulin secretion indexes were significantly lower in the HFD (P = 0.01 and 0.002) and HFDEx trials (P = 0.05 and 0.008) than in the ND trial.

Conclusion

A single bout of aerobic exercise did not improve the short-term HFD-induced aggravation of postprandial glucose and insulin metabolism during the OGTT. However, it did normalize the increased postprandial GLP-1 level induced by HFD.     

Coffee and green tea consumption is associated with insulin resistance in Japanese adults

Objective

Higher coffee and green tea consumption has been suggested to decrease risk of type 2 diabetes, but their roles in insulin resistance (IR) and insulin secretion remain unclear. This study examined the association between habitual consumption of these beverages and markers of glucose metabolism in a Japanese working population.

Materials/Methods

Participants were 1440 Japanese employees (1151 men and 289 women) aged 18–69 years. Consumption of coffee and green tea was ascertained via a validated brief diet history questionnaire. Multilevel linear regression was used to estimate means (95% confidence intervals) of fasting insulin, fasting plasma glucose, homeostatic model assessment of IR (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β) and glycated hemoglobin (HbA1c) with adjustment for potential confounding variables.

Results

Coffee consumption was significantly, inversely associated with HOMA-IR (P for trend = 0.03), and the association appeared to be confined to overweight subjects (BMI ≥ 25 kg/m²) (P for trend = 0.01, P for interaction = 0.08). Unexpectedly, green tea consumption was positively associated with HOMA-IR (P for trend = 0.02), though there was no dose–response relationship among daily consumers of green tea. Neither coffee nor green tea consumption was associated with HOMA-β and HbA1c.

Conclusions

Our findings indicate that coffee consumption may be associated with decreased IR, but not with insulin secretion. The positive association between green tea consumption and IR warrants further investigation.     

Eight weeks of treatment with long-acting GLP-1 analog taspoglutide improves postprandial insulin secretion and sensitivity in metformin-treated patients with type 2 diabetes

Objective

Loss of pancreatic function is pivotal to the deterioration of fasting and postprandial glycemic control in type 2 diabetes (T2D). We evaluated the effects of a long-acting, human glucagon-like peptide-1 analog, taspoglutide, added to metformin, on pancreatic function and peripheral insulin sensitivity.

Materials/methods

We studied 80 T2D patients inadequately controlled [glycosylated hemoglobin (HbA_1c), 7.0%–9.5%] receiving stable metformin for ≥ 12 weeks. They were a subset of participants to a phase 2 trial that received also a 240-min mixed-meal tolerance test (MTT) at baseline and study end. Patients received once weekly (QW) sc injection of taspoglutide 5, 10, or 20 mg (n = 21, 19, or 19), or placebo (n = 21), plus metformin, for 8 weeks. We measured postprandial plasma glucose (PPG) and insulin profiles, insulin secretion rate (ISR), oral glucose insulin sensitivity (OGIS) index; β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios, and insulin sensitivity-to-insulin resistance (or disposition) index.

Results

After 8 weeks of treatment, taspoglutide 5, 10, and 20 mg QW doses vs. placebo improved mean PPG_{0–240 min} (relative change from baseline: − 22.1%, − 25.9%, and − 22.9% vs. − 8.1%; P < 0.005) and mean postprandial ISR_{0–240 min} (+ 14%, + 18%, and + 23% vs. + 1%; P < 0.005 vs dose). Taspoglutide at 20 mg QW dose also resulted in improvements from baseline in OGIS, β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios and the disposition index during the MTT.

Conclusion

Taspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin.     

A short message service (SMS) intervention to prevent diabetes in Chinese professional drivers with pre-diabetes: A pilot single-blinded randomized controlled trial

Aim

To determine the efficacy of delivering short-message service (SMS) to provide diabetes-related information in reducing the risk of developing diabetes in Chinese professional drivers with pre-diabetes.

Methods

A pilot single-blinded randomized controlled trial was conducted in Hong Kong between 05/2009 and 04/2012. Professional drivers with impaired glucose tolerance (IGT) were randomly allocated to either a SMS group receiving messages comprising knowledge and lifestyle modification on diabetes or to a control group with usual care. Primary outcomes were the incidence rate of diabetes mellitus over 12 and 24 months period.

Results

Fifty-four, out of 104 professional drivers recruited, were randomly allocated to intervention group. Fewer subjects developed diabetes at 12 months in intervention group (5.56%) compared to control group (16.00%). Relative risk (RR) of diabetes onset was 0.35 (95%CI: 0.10–1.24) and the number needed to treat (NNT) for preventing one diabetes was 9.57. At 24 months, RR increased to 0.62 (95%CI: 0.24–1.61) with a NNT of 10.58. Logistic regression showed a significant odds ratio of 0.04 (P = 0.021) for intervention group compared to control group at 12-month follow-up for completers and a non-significant odds ratio of 0.34 (P = 0.303) at 24-month follow-up.

Conclusions

The SMS program proved to have potential to reduce the risk of developing diabetes at 12 months but additional measures should be integrated to prevent or delay disease progression.     

The one year exercise and lifestyle intervention program KLAKS: Effects on anthropometric parameters,cardiometabolic risk factors and glycemic control in childhood obesity

Objective

Regular physical exercise within structured lifestyle programs may improve weight status and minimize metabolic risk factors in childhood obesity. The aim of this study was to evaluate the effect of the one-year combined physical exercise/lifestyle program KLAKS on anthropometric and metabolic parameters and glycemic control in childhood obesity.

Materials and Methods

142 overweight/obese (BMI > 90th percentile) candidates (7–18 years) were enrolled, 115 participants completed the program. Anthropometrics and biochemical parameters were obtained at beginning and completion. An oral glucose tolerance test (OGTT) was performed in a subgroup of participants. Course of glucose and insulin levels within OGTT was correlated with several parameters and is reported here for those who completed the program.

Results

The mean standard deviation scores (SDS) decreased significantly for BMI, waist circumference, waist-to-height ratio (WHtR) and percentage body fat (all p ≤ 0.01). Improved metabolic risk markers included mean glucose levels within an OGTT at follow-up compared to baseline (p < 0.0001) and HbA1c (p = 0.05) as well as indications of improvement for gamma-glutamyl-transferase and free fatty acids.

Conclusions

The one-year combined exercise/lifestyle program KLAKS significantly improves markers of obesity and glycemic control. Impaired cardiometabolic risk markers, even subclinical, are also favorably influenced by program participation.     

Alexithymia impact on type 1 and type 2 diabetes: A case-control study

Objectives

This paper focus on studying the prevalence of alexithymia in diabetes type 1 and type 2 and its impact on diabetes's clinical and therapeutic characteristics. We also studied the relationship between alexithymia and emotional disorders in diabetics.

Materials and methods

The study involved a sample of 125 diabetic patients, among whom 50 had type 1 and 75 had type 2 diabetes mellitus compared with respectively 70 and 52 control subjects matched for age and sex. Alexithymia was assessed using the Toronto Alexithymia Scale, while emotional disorders were evaluated using the Hospital Anxiety and Depression Scale.

Results

Type 1 diabetics were more alexithymic than controls while type 2 diabetics had higher cognitive component score than control subjects. Alexithymic type 1 diabetics had a higher average of fasting blood sugar than non-alexithymic patients did (P = 0.021). Moreover, with type 1 diabetes, erectile dysfunction was associated with difficulties in identifying feelings (P = 0.012). We found that the presence of depression was a predictor of alexithymia in type 1 diabetes (β = 1.78, P = 0.04) and the presence of psychiatric history was indicative of the presence of alexithymia in type 2 diabetes (β = 2.09, P = 0.042).

Conclusion

Given the impact of alexithymia on diabetes types 1 and 2, the detection and treatment of alexithymic subjects are important for a better prognosis of diabetic disease.     

Evaluation of the relationship between weight change and glycemic control after initiation of antidiabetic therapy in patients with type 2 diabetes using electronic medical record data

Aims

This study evaluates the relationship between HbA1c and weight change outcomes by anti-diabetic weight-effect properties in patients newly treated for type 2 diabetes; a relationship not previously characterized.

Methods

Electronic medical records of patients with type 2 diabetes newly prescribed anti-diabetic monotherapy were assessed to identify HbA1c goal attainment [(<53 mmol/mol)] and weight change at 1-year. Anti-diabetics were categorized by weight-effect properties: weight-gain (sulfonylureas, thiazolidinediones) and weight-loss/neutral (metformin, DPP-4 inhibitors, GLP-1 agonists). Logistic regression analyses identified likelihood of attaining HbA1c goal or ≥3% weight loss by anti-diabetic category controlling for baseline characteristics. MANOVA was used to identify correlation between changes in weight and HbA1c.

Results

The study included 28,290 patients. Mean age ± sd was 61 years ± 11.8. Baseline HbA1c was 7.4% ± 1.6 (57 mmol/mol ± 17); 67.3% were prescribed a weight-loss/neutral anti-diabetic. At 1-year, more patients in the weight-loss/neutral anti-diabetic category lost weight (≥3%) than in the weight-gain anti-diabetic category (40.4% vs. 24.2%, p < 0.001) or had an HbA1c < 7.0% (<53 mmol/mol) (71.1% vs. 63.8%, p < 0.001). Those prescribed a weight-gain anti-diabetic were 53% less likely to lose weight and 29% less likely to be at HbA1c goal than those prescribed a weight-loss/neutral anti-diabetic (p < 0.001). Weight loss and HbA1c outcomes were significantly correlated (p < 0.001).

Conclusions

Weight loss of ≥3% was associated with better glycemic control in patients newly treated for type 2 diabetes. Anti-diabetics associated with weight-loss/neutrality were associated with greater weight loss and HbA1c goal attainment and may facilitate efforts to co-manage weight and glycemia in the ambulatory-care setting.     

Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24 week,double-blind,randomized Phase 3 trial

Background

Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy.

Methods

In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events ≥ 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1­mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.

Results

Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and 138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001). At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients, respectively).

Conclusions

Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.     

Impact of low-density lipoprotein cholesterol on cardiovascular outcomes in people with type 2 diabetes: A meta-analysis of prospective cohort studies

Aims

To estimate the prospective association of low-density lipoprotein (LDL) cholesterol on cardiovascular disease (CVD) risk among people with type 2 diabetes.

Methods

We used extensive literature searching strategies to locate prospective cohort studies that reported LDL cholesterol levels as a risk factor for cardiovascular events. We conducted meta-analytic procedures for two outcomes: incident CVD and CVD mortality.

Results

A total of 16 studies were included in this analysis with a mean follow-up range of 4.8–11 years. The pooled relative risk associated with a 1 mmol/L increase in LDL cholesterol in people with type 2 diabetes was 1.30 (95% confidence interval [CI], 1.19–1.43) for incident CVD, and 1.50 (95% CI, 1.25–1.80) for CVD mortality, respectively. Subgroup analyses showed that for incident CVD, the pooled relative risk was 1.28 (95% CI, 1.17–1.41) for 7 studies adjusted for blood pressure and/or glucose concentration (or insulin concentration, glycated hemoglobin) and 1.40 (95% CI, 1.05–1.86) for 3 studies that did not adjust for these variables.

Conclusions

Our study demonstrates that LDL cholesterol was associated with an increased risk for cardiovascular outcomes in people with type 2 diabetes, independent of other conventional risk factor.     

Adiponectin improves endothelial dysfunction caused by elevated FFAs levels, partially through cAMP-dependent pathway

Aims/hypothesis

The aim of this study was to investigate clinical spectrum of hepatocyte nuclear factor-1β (HNF-1β) mutation in Chinese diabetic patients with renal dysfunction and/or structure abnormalities.

Materials and methods

A total of 104 diabetic patients with renal structural abnormalities and/or non-diabetic renal dysfunction were recruited and HNF-1β mutation was screened by direct sequencing.

Results

Three heterozygous missense mutations including c.494G>A (p.R165H), c.662A>T (p.D221V) and c.780G>C (p.E260D) were identified. Progression of diabetes and mild decline of renal function were observed in the mutation carriers during the follow-up. The p.R165H mutation carrier had severe β-cell dysfunction and different extrapancreatic phenotypes. Compared with type 2 diabetes and normoglycemics, the p.R165H mutation carrier had a lower basal C-peptide (0.30, 0.61 ± 0.07 and 0.50 ± 0.04 nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively) and low values of acute C-peptide response to arginine (0.15, 0.48 ± 0.18 and 0.76 ± 0.08 nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively).

Conclusion

Patients with the HNF-1β mutation in our population can have different pancreatic and extrapancreatic phenotypes. The exact contributions of mutations to the phenotypes await functional confirmation.     

Changes of serum omentin-1 levels in normal subjects,type 2 diabetes and type 2 diabetes with overweight and obesity in Chinese adults

Purpose

Omentin-1 has been identified as interesting novel adipokines that may modulate insulin action. Its exact biological function is unclear. The aim of this study is to assay the levels of serum omentin-1 in normal subjects and type 2 diabetes mellitus (T2DM) with normal weight, overweight and obesity and to analyze the relationship between serum omentin-1 levels with body mass index (BMI), waist to hip ratio (WHR), glycosylated hemoglobin (HbA1c), plasma glucose, insulin resistance index (HOMA-IR) and serum lipid levels.

Methods

There are eighty newly diagnosed type 2 diabetes patients, thirty-five type 2 diabetes patients with normal weight, twenty-nine type 2 diabetes patients with overweight, sixteen type 2 diabetes patients with obesity, and forty healthy control subjects were enrolled in this study. The levels of plasma glucose at fasting and 2-hour postprandial blood glucose and fasting serum levels of insulin, omentin-1and HbA1c were measured. HOMA-IR was calculated.

Results

Serum omentin-1 levels were found to be significantly decreased in type 2 diabetes patients with normal weight (821.16 ± 312.50 ng/L), in type 2 diabetes patients with overweight (748.00 ± 322.51 ng/L), and in type 2 diabetes patients with obesity (530.44 ± 357.35 ng/L) compared with healthy control subjects (994.71 ± 435.90 ng/L) at P < 0.05. The level of serum omentin-1 was negatively correlated to BMI, HOMA-IR, WHR, fasting insulin (FINS), fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2HPG), triglycerides (TG), and positively correlated to high-density lipoprotein (HDL). BMI was independent related factor that influenced the levels of serum omentin-1.

Conclusion

Decreased omentin-1 levels may contribute to the development of insulin resistance, T2DM and particularly to obesity in Chinese adults, however, its role in these diseases needs to be fully elucidated.     

Irisin in response to acute and chronic whole-body vibration exercise in humans

Objective

Irisin is a recently identified myokine, suggested to mediate the beneficial effects of exercise by inducing browning of white adipocytes and thus increasing energy expenditure. In humans, the regulation of irisin by exercise is not completely understood. We investigated the effect of acute and chronic whole-body vibration exercise, a moderate-intensity exercise that resembles shivering, on circulating irisin levels in young healthy subjects.

Materials/Methods

Healthy untrained females participated in a 6-week program of whole-body vibration exercise training. Blood was drawn before and immediately after an acute bout of exercise at baseline (week 0) and after 6 weeks of training.

Results

The resting irisin levels were not different at baseline (week 0) and after 6 weeks of training. At both 0 and 6 weeks of training, an acute bout of vibration exercise significantly elevated circulating irisin levels by 9.5% and 18.1%, respectively (p = 0.05 for the percent change of irisin levels).

Conclusions

Acute bouts of whole-body vibration exercise are effective in increasing circulating irisin levels but chronic training does not change levels of baseline irisin levels in humans.     

Variations in erythrocyte antioxidant levels and lipid peroxidation status and in serum lipid profile parameters in relation to blood haemoglobin A1c values in individuals with type 2 diabetes mellitus

Aims

The present study aimed to evaluate the antioxidant and lipid peroxidation status in erythrocytes and serum lipid profile parameters, in relation to haemoglobin A1c (HbA1c) concentrations, in patients with type 2 diabetes mellitus and in normal healthy individuals.

Methods

Sixty test individuals with diabetes and 15 control individuals were categorized as: Group I, control (non-diabetes); Group II, individuals with diabetes with HbA1c levels ≤7.0% (53 mmol/mol); Group III, individuals with diabetes with HbA1c levels between 7.1 and 8.0% (54 and 64 mmol/mol); Group IV, individuals with diabetes with HbA1c levels between 8.1 and 9.0% (65 and 75 mmol/mol); Group V, individuals with diabetes with HbA1c levels >9.0% (75 mmol/mol). Blood samples were collected to measure: blood glucose and HbA1c levels; haemolysate levels of enzymatic antioxidants and non-enzymatic antioxidants and malondialdehyde (MDA); and serum total cholesterol, triglyceride and high-density lipoprotein (HDL)-cholesterol levels. Correlations between blood HbA1c values and all parameters were sought.

Results

Significantly lower mean activities/levels of antioxidant parameters and significantly higher mean levels of MDA were noted in haemolysate samples from patients with diabetes than in those from control individuals. Significantly higher mean serum concentrations of total cholesterol and triglycerides and significantly lower mean concentrations of HDL-cholesterol were noted in patients with diabetes than in control individuals. Further, moderate to strong correlations were observed between values of antioxidants, MDA and lipid profile parameters and blood concentrations of HbA1c.

Conclusion

These results suggest that HbA1c values may be potentially useful not only to indicate long-term glycemic control to indicate onset of complications at a clinically detectable level and molecular level.     

Antibodies to malondialdehyde oxidized low-density lipoproteins predict long term cardiovascular mortality in high risk patients

Aims

Antibodies to oxidized low-density lipoproteins (oxLDLAbs) are detectable in the serum of patients with and without atherosclerosis, but it is unclear if they play a pathogenic or a protective role in atherogenesis or if they are simply a marker of atherosclerosis. Therefore, in a prospective cohort study we investigated if oxLDLAbs titer predicts cardiovascular (CV) events in high-risk coronary artery disease patients.

Methods and results

The titer of IgG antibodies to malondialdehyde modified oxidized low-density lipoproteins was measured in 748 randomly selected patients of the GENICA study who underwent coronary angiography and assessment of incident CV events at follow-up. Patients were classified by oxLDLAbs into a low and a high titer group, corresponding to the first three and the last quartile, respectively. Cardiovascular event-free survival was compared between oxLDLAbs groups by Kaplan–Meier and multivariate technique including propensity score matching analysis. During long-term follow-up (median 7.2 years) CV deaths were observed in 65 patients (11.6%), more commonly in the high than in the low oxLDLAbs group (patients free from CV death 83.1% vs. 89% respectively, p = 0.025). The incidence of CV events was also higher in the former than in latter (event-free survival 69.2% vs. 77.7% respectively, p = 0.030).

Conclusions

An oxLDLAbs titer above the 75th percentile is a marker of LDL oxidation which predicts a worse CV prognosis at long term follow-up in high-risk Caucasian patients referred for coronary angiography.