During our phylogenetic evolution we have selected genes, the so called thrifty genes, that can help to maximize the amount of energy stored from every consumed calorie. An imbalance in the amount of stored calories can lead to many diseases. In the early 80’s the distinguished English epidemiologist David Barker, formulated a hypothesis suggesting that many events that occur during the intrauterine life and early in infancy can influence the occurrence of many diseases that will develop in adulthood. This theory proposes that under-nutrition and other insult or adverse stimulus in utero and during infancy can permanently change the body’s structure, physiology and metabolism. The lasting or lifelong effects of under-nutrition will depend on the period in the development at which it occurs. The clues that led Barker to his conclusions started to be discovered when he was studying the temporal trends in the incidence of ischemic heart disease in England and Wales. Examining data found in The Hertfordshire records, collected in the beginning of the last century, he found that the rates of mortality by ischemic heart disease was much higher in children born in less affluent counties and mostly in those with low birth weight. After his initial findings a myriad of diseases have been found to be linked to low birth weight and under-nutrition in utero and in the neonatal period. These diseases were then nominated adult diseases with fetal origin. Epidemiological studies that led to these findings suggest that in utero and early postnatal life have critical importance for long-term programming of health and disease, opening unique chances for primary prevention of chronic diseases.
Current gold standard therapeutic strategies for T2DM target insulin resistance or β cell dysfunction as their core mechanisms of action. However, the use of traditional anti-diabetic drugs, in most cases, does not significantly reduce macrovascular morbidity and mortality. Among emerging anti-diabetic candidates, glucagon like peptide-1 (GLP-1) based therapies carry special cardiovascular implications, exerting both direct as well as indirect effects. The direct cardiovascular effects of GLP-1 and its analogs remain the focus of this review.
The Brazilian Study on the Practice of Diabetes Care main objective was to provide an epidemiological profile of individuals with type 1 and 2 diabetes mellitus (DM) in Brazil, concerning therapy and adherence to international guidelines in the medical practice.
This observational, cross-sectional, multicenter study collected and analyzed data from individuals with type 1 and 2 DM attending public or private clinics in Brazil. Each investigator included the first 10 patients with type 2 DM who visited his/her office, and the first 5 patients with type 1 DM.
A total of 1,358 patients were analyzed; 375 (27.6%) had type 1 and 983 (72.4%) had type 2 DM. Most individuals were women, Caucasian, and private health care users. High prevalence rates of hypertension, dyslipidemia and central obesity were observed, particularly in type 2 DM. Only 7.3% and 5.1% of the individuals with types 1 and 2 DM, respectively, had optimal control of blood pressure, plasma glucose and lipids. The absence of hypertension and female sex were associated with better control of type 1 DM and other cardiovascular risk factors. In type 2 DM, older age was also associated with better control.
Female sex, older age, and absence of hypertension were associated with better metabolic control. An optimal control of plasma glucose and other cardiovascular risk factors are obtained only in a minority of individuals with diabetes. Local numbers, compared to those from other countries are worse.
Diabetes mellitus; Risk factors; Cardiovascular disease
Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians.
A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV ≥ 12 m/s.
In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals.
These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.
Arterial stiffness; Diabetes mellitus; Hypertension; Brazilian population
We aimed to explore the association between presence and number of components of the Metabolic Syndrome (MetS) and subclinical atherosclerosis outcomes (common carotid intima media thickness, plaque presence and sum of plaque area) in both the carotid and femoral bifurcations.
Cross-sectional analysis of 771 volunteers from the ongoing epidemiological Cyprus Study (46% male; mean age = 60.1 ± 9.8). (a) Carotid intima-media thickness (IMTcc), (b) sum of plaque area in the carotid bifurcations (sum of the largest plaques in each carotid bifurcation-SPAcar), (c) sum of plaque area in the femoral bifurcations (sum of the largest plaques in each femoral bifurcation-SPAfem) and (d) sum of plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured at baseline using ultrasound. Presence and number of components of the MetS was ascertained using the National Cholesterol Education Program ATPIII definition and their association tested using multivariable regression models.
MetS was present in 259 (33.6%) individuals and was associated with a 0.02 mm increase in IMTcc (95% CI: 0.00 to 0.04, p = 0.047) after adjustment for age, sex, family history of CVD, alcohol consumption (BU/week) and smoking (pack-years). Each additional component of the MetS was associated with a 16% higher SPA (95% CI: 6.8% to 25.2%, pfor trend = 0.001), a 10% higher SPAcar (95% CI: 5% to 24%, pfor trend = 0.003) and a 14% higher SPAfem in the adjusted model.
We confirm an association between the MetS and IMTcc as well as report for the first time an association between the MetS and its components and femoral plaque area, in a general population over 40 years of age. Having any risk factors for the MetS increases the risk for subclinical atherosclerosis, with the risk increasing with each additional component. Using the dichotomous definition of the MetS may be overlooking the risk for subclinical atherosclerosis –and by inference future cardiovascular events- associated with having less than 3 risk factors.
Metabolic syndrome; Metabolic syndrome components; Atherosclerotic plaques; Plaque area; Femoral; Carotid; IMT
The aim of this study is to compare the efficacy of intensification of insulin treatment with insulin glargine and biphasic human insulin in patients with type 2 diabetes on concomitant therapy with oral antidiabetic drugs (OAD) in daily clinical practice.
A retrospective multicentre parallel two-arm study included 301 patients with type 2 diabetes already on treatment with biphasic human insulin twice daily (bd) in combination with OAD. Data were collected retrospectively from 142 patients who had been switched from biphasic human insulin to insulin glargine in a period of 6–12 months prior to their inclusion (active group) and compared to data collected retrospectively from 159 patients who continued treatment with biphasic human insulin bd for the same time period (control group). Our primary objective was to examine the efficacy of the two treatments, assessed as change in HbA1c. Secondary objectives were to examine for changes in fasting blood glucose (FBG), body weight, treatment with OAD or fast-acting insulin and safety, by assessing the frequency and severity of hypoglycaemic episodes.
At the end of the study there was a significant reduction in HbA1c in both arms. The least squares (LS) mean [(95% confidence intervals (CI)] reduction in HbA1c was -1.13 (-0.96 to -1.30)% in the active and -0.59 (-0.41to -0.77)% in the control group [LS mean treatment difference 0.53 (0.31-0.76)%, p < 0.001]. Similarly, fasting blood glucose declined significantly in both arms. The LS mean decline in FBG was -47.02 (-37.89 to -56.14) mg/dl in the active and -19.73 (-11.57 to -27.89) mg/dl in the control group [LS mean treatment difference 27.85 (15.74-39.95) mg/dl, p < 0.001]. No significant difference in hypoglycaemic episodes and in body weight was found. In the active group, more patients received rapid-acting pre-meal insulin and used insulin secretagogues drugs.
Glargine alone or in combination with fast acting insulin is more effective in reducing glycaemia than biphasic human insulin alone or in combination with fast acting insulin in patients with type 2 diabetes without increase in hypoglycaemic episodes or body weight.
Biphasic human insulin; Insulin glargine; Glycaemic control; Hypoglycaemia; Body weight
The worldwide epidemic of diabetes and obesity has resulted in a rapid upsurge in the prevalence of metabolic syndrome (MetS). MetS makes the individual liable to endothelial dysfunction which can initiate sexual dysfunction (SD). This study assessed the association between MetS and SD among clinically diagnosed diabetic subjects in Tema, Greater Accra Region of Ghana.
Sexual functioning was assessed using Golombok Rust Inventory of Sexual Satisfaction in 300 consecutive diabetic men visiting the diabetic clinic of Tema General Hospital between November, 2010 and March, 2011. Anthropometric data including waist and hip circumference as well as blood pressure were measured. The levels of fasting blood glucose and serum lipid profile were assessed. All the men had a steady heterosexual relationship for at least 2 years before enrolment in the study.
The response rate was 91.3% out of the 300 subjects recruited for the study. Those with SD were significantly older and had diabetes for a longer period as compared to those without SD. The prevalence of MetS as defined by the various criteria was 78.8%, 43.4% and 51.8% for WHO, NCEP ATP III and IDF respectively. Central obesity (p = 0.0482) and raised blood pressure (p = 0.0309) are the significant MetS components when the studied population was stratified according to sexual functioning. Generally, SD as well as its sub-scales correlate positively with age, blood pressure, duration of diabetes and MetS score. Whereas TC and LDL-c correlated positively with non-communication, TG correlates positively with avoidance and infrequency.
SD and its sub-scales have a direct relationship with duration of diabetes, blood pressure and MetS score from this study. Central obesity and raised blood pressure seem to be the link between MetS and SD among this clinically diagnosed diabetic subjects.
The phosphodiesterase inhibitor cilostazol has beneficial effects on atherosclerosis by virtue of vasodilatory and antiplatelet effects. However, less is known about the effect of cilostazol on arterial stiffness and biochemical markers related to vascular inflammation and endothelial dysfunction in type 2 diabetic patients with metabolic syndrome.
In this randomized, double-blind, crossover trial, 45 diabetic patients with metabolic syndrome were randomly assigned to either the cilostazol group (50 mg for 2 weeks, 100 mg for 6 weeks) or placebo group for an 8-week treatment phase, and then crossed over. Brachial-ankle pulse wave velocity (baPWV) and serum levels of inflammatory cytokines and vascular cellular adhesion molecules were measured before and after each treatment phase.
Compared with the placebo group, the mean baPWV did not improve in the cilostazol group (mean difference 31.42 cm/sec, 95% CI −55.67 to 118.5). Cilostazol treatment significantly reduced soluble vascular cellular adhesion molecule-1 (sVCAM-1) level (from 1288.7 ± 285.6 to 1168.2 ± 252.3 ng/dL, P = 0.0003), and there was also significant mean difference between groups (mean difference 105.18 ng/dL, 95% CI 10.65 to 199.71). However, other biochemical markers including lipid profiles, high sensitivity C-reactive protein, adiponectin, interleukin-6, tumor necrosis factor-alpha, monocyte chemotactic protein-1, and soluble intercellular adhesion molecule-1 did not improve with cilostazol treatment.
Cilostazol treatment significantly reduced serum sVCAM-1 level, but this short term treatment was not associated with beneficial effect on arterial stiffness and other inflammatory markers.
(Clinical trial reg. no. NCT00573950, clinicaltrials.gov.)
Cilostazol; Phosphodiesterase inhibitor; Arterial stiffness; Vascular adhesion molecules; Type 2 diabetes; Metabolic syndrome
Quantitation of β-cell function is critical in better understanding of the dynamic interactions of insulin secretion, clearance and action at different phases in the progression of diabetes. The present study aimed to quantify β-cell secretory function independently of insulin sensitivity in the context of differential metabolic clearance rates of insulin (MCRI) in nonhuman primates (NHPs).
Insulin secretion rate (ISR) was derived from deconvolution of serial C-peptide concentrations measured during a 5 stage graded glucose infusion (GGI) in 12 nondiabetic (N), 8 prediabetic or dysmetabolic (DYS) and 4 overtly diabetic (DM) cynomolgus monkeys. The characterization of the monkeys was based on the fasting glucose and insulin concentrations, glucose clearance rate measured by intravenous glucose tolerance test, and insulin resistance indices measured in separate experiments. The molar ratio of C-peptide/insulin (C/I) was used as a surrogate index of hepatic MCRI.
Compared to the N monkeys, the DYS with normal glycemia and hyperinsulinemia had significantly higher basal and GGI-induced elevation of insulin and C-peptide concentrations and lower C/I, however, each unit of glucose-stimulated ISR increment was not significantly different from that in the N monkeys. In contrast, the DM monkeys with β-cell failure and hyperglycemia had a depressed GGI-stimulated ISR response and elevated C/I.
The present data demonstrated that in addition to β-cell hypersecretion of insulin, reduced hepatic MCRI may also contribute to the development of hyperinsulinemia in the DYS monkeys. On the other hand, hyperinsulinemia may cause the saturation of hepatic insulin extraction capacity, which in turn reduced MCRI in the DYS monkeys. The differential contribution of ISR and MCRI in causing hyperinsulinemia provides a new insight into the trajectory of β-cell dysfunction in the development of diabetes. The present study was the first to use the GGI and C-peptide deconvolution method to quantify the β-cell function in NHPs.
Insulin secretion rate; C-peptide; Deconvolution; Graded glucose infusion; GGI; Insulin resistance; β-cell failure; Diabetes; Hepatic insulin extraction; Nonhuman primate
Glucose variability could be an independent risk factor for diabetes complications in addition to average glucose. The deficiency in islet β cell secretion and insulin sensitivity, the two important pathophysiological mechanisms of diabetes, are responsible for glycemic disorders. The oral disposition index evaluated by product of insulin secretion and sensitivity is a useful marker of islet β cell function. The aim of the study is to investigate glycemic variability in relation to oral disposition index in the subjects across a range of glucose tolerance from the normal to overt type 2 diabetes.
75-g oral glucose tolerance test (OGTT) was performed in total 220 subjects: 47 with normal glucose regulation (NGR), 52 with impaired glucose metabolism (IGM, 8 with isolated impaired fasting glucose [IFG], 18 with isolated impaired glucose tolerance [IGT] and 26 with combined IFG and IGT), 61 screen-diagnosed diabetes by isolated 2-h glucose (DM2h) and 60 newly diagnosed diabetes by both fasting and 2-h glucose (DM). Insulin sensitivity index (Matsuda index, ISI), insulin secretion index (ΔI30/ΔG30), and integrated β cell function measured by the oral disposition index (ΔI30/ΔG30 multiplied by the ISI) were derived from OGTT. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SD), mean of blood glucose (MBG), high blood glucose index (HBGI), continuous overlapping net glycemic action calculated every 1 h (CONGA1), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE).
From the NGR to IGM to DM2h to DM group, the respective values of SD (mean ± SD) (0.9 ± 0.3, 1.5 ± 0.5, 1.9 ± 0.6 and 2.2 ± 0.6 mmol/), MBG (5.9 ± 0.5, 6.7 ± 0.7, 7.7 ± 1.0 and 8.7 ± 1.5 mmol/L), HGBI [median(Q1–Q3)][0.8(0.2–1.2), 2.0(1.2–3.7), 3.8(2.4–5.6) and 6.4(3.2–9.5)], CONGA1 (1.0 ± 0.2, 1.3 ± 0.2, 1.5 ± 0.3 and 1.8 ± 0.4 mmol/L), MODD (0.9 ± 0.3, 1.4 ± 0.4, 1.8 ± 0.7 and 2.1 ± 0.7 mmol/L) and MAGE (2.1 ± 0.6, 3.3 ± 1.0, 4.3 ± 1.4 and 4.8 ± 1.6 mmol/L) were all increased progressively (all p < 0.05), while their oral disposition indices [745(546–947), 362(271–475), 203(134–274) and 91(70–139)] were decreased progressively (p < 0.05). In addition, SD, MBG, HGBI, CONGA1, MODD and MAGE were all negatively associated with the oral disposition index in each group (all p < 0.05) and in the entire data set (r = −0.66, –0.66, –0.72, –0.59, –0.61 and −0.65, respectively, p < 0.05).
Increased glycemic variability parameters are consistently associated with decreased oral disposition index in subjects across the range of glucose tolerance from the NGR to IGM to DM2h to DM group.
Glycemic variability; Continuous glucose monitoring; Oral disposition index; Type 2 diabetes
Diabetes mellitus is a chronic disease that necessitates continuing treatment and patient self-care education. Monitoring of blood glucose to near normal level without hypoglycemia becomes a challenge in the management of diabetes. Although self monitoring of blood glucose (SMBG) can provide daily monitoring of blood glucose level and help to adjust therapy, it cannot detect hypoglycemic unawareness and nocturnal hypoglycemia which occurred mostly in T1DM pediatrics. Continuous glucose monitoring (CGM) offers continuous glucose data every 5 minutes to adjust insulin therapy especially for T1DM patients and to monitor lifestyle intervention especially for T2DM patients by care providers or even patients themselves. The main objective of this study was to assess the effects of continuous glucose monitoring (CGM) on glycemic control in Type 1 diabetic pediatrics and Type 2 diabetic adults by collecting randomized controlled trials from MEDLINE (pubmed), SCOPUS, CINAHL, Web of Science and The Cochrane Library up to May 2013 and historical search through the reference lists of relevant articles. There are two types of CGM device: real-time CGM and retrospective CGM and both types of the device were included in the analysis. In T1DM pediatrics, CGM use was no more effective than SMBG in reducing HbA1c [mean difference – 0.13% (95% CI -0.38% to 0.11%,]. This effect was independent of HbA1c level at baseline. Subgroup analysis indicated that retrospective CGM was not superior to SMBG [mean difference -0.05% (95% CI -0.46% to 0.35%)]. In contrast, real-time CGM revealed better effect in lowering HbA1c level compared with SMBG [mean difference -0.18% (95% CI -0.35% to -0.02%, p = 0.02)]. In T2DM adults, significant reduction in HbA1c level was detected with CGM compared with SMBG [mean difference – 0.31% (95% CI -0.6% to -0.02%, p = 0.04)].
This systematic review and meta-analysis suggested that real-time CGM can be more effective than SMBG in T1DM pediatrics, though retrospective CGM was not. CGM provided better glycemic control in T2DM adults compared with SMBG.
Systematic review; Continuous glucose monitoring (CGM); T1DM, Type 1 diabetes; T2DM, Type 2 diabetes; SMBG, Self monitoring of blood glucose
Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it.
We studied 36 young Hispanic adults without diabetes (ages 18–40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups.
Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese.
Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.
Diabetes; Cardiovacular disease; Endothelial; ICAM-1; Hispanics; Prevention
To investigate the predictive value of different biomarkers for the incidence of type 2 diabetes mellitus (T2DM) in subjects with metabolic syndrome.
A prospective study of 525 non-diabetic, middle-aged Lithuanian men and women with metabolic syndrome but without overt atherosclerotic diseases during a follow-up period of two to four years. We used logistic regression to develop predictive models for incident cases and to investigate the association between various markers and the onset of T2DM.
Fasting plasma glucose (FPG), body mass index (BMI), and glycosylated haemoglobin can be used to predict diabetes onset with a high level of accuracy and each was shown to have a cumulative predictive value. The estimated area under the receiver-operating characteristic curve (AUC) for this combination was 0.92. The oral glucose tolerance test (OGTT) did not show cumulative predictive value. Additionally, progression to diabetes was associated with high values of aortic pulse-wave velocity (aPWV).
T2DM onset in middle-aged metabolic syndrome subjects can be predicted with remarkable accuracy using the combination of FPG, BMI, and HbA1c, and is related to elevated aPWV measurements.
Metabolic syndrome; Type 2 diabetes mellitus; Risk assessment; Biomarkers; Arterial markers; Predictive models
The landmark Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) placed a new spotlight on thiazide diuretics as the first-line therapy for hypertension. This is concerning as thiazide-diuretics may contribute to comorbidities associated with the current epidemic of obesity. Previous randomized clinical trials have linked thiazide diuretic treatment to insulin resistance, metabolic syndrome, and increased incidence of type 2 diabetes.
This proof of concept, longitudinal, randomized, double–blind study evaluated the effects of the angiotensin II receptor blocker Valsartan and the specific thiazide diuretic Hydrochlorothiazide (HCTZ) on hepatic triglyceride level (primary outcome), as well as triglyceride levels within other organs including the heart, skeletal muscle, and pancreas. Additionally, we evaluated whether myocardial function, insulin sensitivity, and insulin secretion were affected by these treatments.
Hepatic TG levels increased by 57% post HCTZ treatment: ∆hTG HCTZ = 4.12% and remained unchanged post Valsartan treatment: ∆hTG V = 0.06%. The elevation of hepatic TG levels after HCTZ treatment was additionally accompanied by a reduction in insulin sensitivity: ∆SI HCTZ = -1.14. Treatment with Valsartan resulted in improved insulin sensitivity: ∆SI V = 1.24. Treatment-induced changes in hepatic TG levels and insulin sensitivity were statistically significant between groups (phTG = 0.0098 and pSI = 0.0345 respectively). Disposition index, DI, remained unchanged after HCTZ treatment: ∆DI HCTZ = -141 but it was increased by a factor of 2 after treatment with Valsartan: ∆DI V =1018). However, the change between groups was not statistically significant. Both therapies did not modify abdominal visceral and subcutaneous fat mass as well as myocardial structure and function. Additionally, myocardial, pancreatic, and skeletal muscle triglyceride deposits remained unchanged in both therapeutic arms.
Our findings are two-fold and relate to hepatic steatosis and insulin sensitivity. HCTZ treatment worsened hepatic steatosis measured as hepatic triglyceride content and reduced insulin sensitivity. Valsartan treatment did not affect hepatic triglyceride levels and improved insulin sensitivity. The results of this study reinforce the message that in patients at risk for type 2 diabetes it is particularly important to choose an antihypertensive regimen that lowers blood pressure without exacerbating patient’s metabolic profile.
Type 2 diabetes; Valsartan; Hydrochlorothiazide; Proton magnetic resonance spectroscopy; Insulin sensitivity; Insulin secretion
Both acute hyperglycemia as diabetes results in an impaired prognosis in ST-elevation myocardial infarction (STEMI) patients. It is unknown whether there is a different prevalence of diabetes and acute hyperglycemia in men and women within age-groups.
Between 2004 and 2010, 4640 consecutive patients (28% women) with STEMI, were referred for primary PCI. Patients were stratified into two age groups, < 65 years (2447 patients) and ≥65 years (2193 patients). Separate analyses were performed in 3901 patients without diabetes. Diabetes was defined as known diabetes or HbA1c ≥6.5 mmol/l at admission.
The prevalence of diabetes was comparable between women and men in the younger age group (14% vs 12%, p = 0.52), whereas in the older age group diabetes was more prevalent in women (25% vs 17% p < 0.001). In patients without diabetes, admission glucose was comparable between both genders in younger patients (8.1 ± 2.0 mmol/l vs 8.0 ± 2.2 mmol/l p = 0.36), but in older patients admission glucose was higher in women than in men (8.7 ± 2.1 mmol/l vs 8.4 ± 2.1 mmol/l p = 0.028). After multivariable analyses, the occurrence of increased admission glucose was comparable between men and women in the younger age group (OR 1.1, 95%CI 0.9-1.5), but increased in women in the older age group (OR 1.3, 95% CI 1.1-1.7). Both diabetes and hyperglycemia were associated with a higher one-year mortality in both men and women.
The differences between men and women in hyperglycemia and diabetes in patients with STEMI are age dependent and can only be observed in older patients. This may have implications for medical treatment and should be investigated further.
STEMI; Gender; Diabetes; Acute hyperglycemia
Our purpose was to develop and test a predictive model of the acute glucose response to exercise in individuals with type 2 diabetes.
Design and methods
Data from three previous exercise studies (56 subjects, 488 exercise sessions) were combined and used as a development dataset. A mixed-effects Least Absolute Shrinkage Selection Operator (LASSO) was used to select predictors among 12 potential predictors. Tests of the relative importance of each predictor were conducted using the Lindemann Merenda and Gold (LMG) algorithm. Model structure was tested using likelihood ratio tests. Model accuracy in the development dataset was assessed by leave-one-out cross-validation.
Prospectively captured data (47 individuals, 436 sessions) was used as a test dataset. Model accuracy was calculated as the percentage of predictions within measurement error. Overall model utility was assessed as the number of subjects with ≤1 model error after the third exercise session. Model accuracy across individuals was assessed graphically. In a post-hoc analysis, a mixed-effects logistic regression tested the association of individuals’ attributes with model error.
Minutes since eating, a non-linear transformation of minutes since eating, post-prandial state, hemoglobin A1c, sulfonylurea status, age, and exercise session number were identified as novel predictors. Minutes since eating, its transformations, and hemoglobin A1c combined to account for 19.6% of the variance in glucose response. Sulfonylurea status, age, and exercise session each accounted for <1.0% of the variance. In the development dataset, a model with random slopes for pre-exercise glucose improved fit over a model with random intercepts only (likelihood ratio 34.5, p < 0.001). Cross-validated model accuracy was 83.3%.
In the test dataset, overall accuracy was 80.2%. The model was more accurate in pre-prandial than postprandial exercise (83.6% vs. 74.5% accuracy respectively). 31/47 subjects had ≤1 model error after the third exercise session. Model error varied across individuals and was weakly associated with within-subject variability in pre-exercise glucose (Odds ratio 1.49, 95% Confidence interval 1.23-1.75).
The preliminary development and test of a predictive model of acute glucose response to exercise is presented. Further work to improve this model is discussed.
Prediction; Exercise; Type 2 Diabetes; Blood Glucose
The aim of this study was to evaluate whether rosuvastatin (HMG-CoA reductase inhibitor) modulates the carbohydrate and lipid metabolism, the development of non-alcoholic fatty liver disease (NAFLD), and the increase in body mass in a model of diet-induced obesity. Male C57Bl/6 mice (3-months-old) were fed a high-fat diet (HF, 60% lipids) or the standard chow (SC, 10% lipids) for 15 weeks. The animals were then treated with 10 mg/kg/day (HF-R10 group), 20 mg/kg/day (HF-R20), or 40 mg/kg/day (HF-R40) of rosuvastatin for five weeks. The HF diet led to glucose intolerance, insulin resistance, weight gain, increased visceral adiposity with adipocyte hypertrophy, and hepatic steatosis (micro and macrovesicular). The rosuvastatin treatment decreased the adiposity and the adipocyte size in the HF-R10 and HF-R20 groups. In addition, rosuvastatin changed the pattern of fat distribution in the HF-R40 group because more fat was stored subcutaneously than in visceral depots. This redistribution improved the fasting glucose and the glucose intolerance. Rosuvastatin also improved the liver morphology and ultrastructure in a dose-dependent manner. In conclusion, rosuvastatin exerts pleiotropic effects through a dose-dependent improvement of glucose intolerance, insulin sensitivity and NAFLD and changes the fat distribution from visceral to subcutaneous fat depots in a mouse model of diet-induced obesity.
Rosuvastatin; Insulin resistance; Adipose tissue; NAFLD
Chronic inflammation is related to both obesity and diabetes. Our aim was to investigate to what extent this inflammation contributes to the association between obesity and diabetes.
Using a case-cohort design, we followed 567 middle-aged individuals who developed diabetes and 554 who did not over 9 years within the ARIC Study. Weighted Cox proportional hazards analyses permitted statistical inference to the entire cohort.
Obese individuals (BMI≥30 kg/m2), compared to those with BMI<25 kg/m2, presented a large increased risk of developing diabetes (HR[obesity]=6.4, 95%CI 4.5–9.2), as did those in the highest (compared to the lowest) quartile of waist circumference (HR[waist]=8.3, 95%CI 5.6–12.3), in analyses adjusted for age, gender, ethnicity, study center, and parental history of diabetes. Notably, further adjustment for adiponectin and inflammation markers halved the magnitude of these associations (HR[obesity]=3.2, 95%CI 2.1–4.7; and HR[waist]=4.2, 95%CI 2.8–6.5). In similar modeling, attenuation obtained by adding fasting insulin, instead of these markers, was only slightly more pronounced HR[obesity]=2.7, 95%CI 1.7–4.1; and HR[waist]=3.6, 95%CI 2.3–5.8).
The marked decrease in the obesity-diabetes association after taking into account inflammation markers and adipokines indicates their major role in the pathways leading to adult onset of diabetes in obese individuals.
Diabetes; Obesity; Inflammation; Adipokines; Humans; Epidemiologic studies
The purpose of the present study was to evaluate the effect and predictive value of metabolic syndrome (MetS) and its components on diastolic heart failure (DHF) in patients at high risk for coronary artery disease (CAD).
Materials and methods
We enrolled 261 patients with normal left ventricular ejection fraction (≥50%) who were scheduled to undergo coronary angiography for suspected myocardial ischemia. They were categorized into three groups (non-MetS, pre-MetS and MetS) based on the number of MetS criteria. Echocardiography was used to assess left ventricular (LV) diastolic function. The association between MetS and DHF was assessed by multivariate logistic regression (MLR) analysis (non-DHF patients as reference group) after controlling for confounders. The predictive performance of the MetS severity score (MSS) was evaluated using the area under the receiver-operating characteristic curve (AUC).
A tendency toward increased DHF prevalence with increasing MSS was found (p < 0.001). MLR analysis showed that in patients with an MSS of 1, the odds ratio (OR) of DHF was 1.60 (95% confidence interval-CI, 1.19–2.16; p = 0.02) compared to non-DHF patients; in patients with MSS ≥4, the OR was 6.61 (95% CI, 4.90–8.90; p < 0.001) compared to non-DHF patients. MSSs strongly predicted DHF (AUC = 0.73, 95% CI, 0.66–0.78, p < 0.001). MLR with MetS components as binary variables showed that blood pressure (BP) and triglycerides (TGs) were significantly associated with DHF (P = 0.001 and 0.043, respectively).
Our findings signify that MetS and its components of BP or TG were associated with DHF in high-risk CAD patients. DHF prevalence tends to increase with increasing MSS that has a high value in predicting DHF in high-risk CAD patients.
Metabolic syndrome; Diastolic heart failure; High-risk patients; Association; Coronary artery disease
High fat feeding increases hepatic fat accumulation and is associated with hepatic insulin resistance. AMP Activated Protein Kinase (AMPK) is thought to inhibit lipid synthesis by the acute inhibition of glycerol-3-phosphate acyltransferase (GPAT) activity and transcriptional regulation via sterol regulatory element binding protein-1c (SREBP-1c).
The purpose of this study was to determine if chronic activation of AMPK prevented an increase in GPAT1 activity in rats fed a high fat diet. Rats were fed a control (C), or a high fat (HF) diet (60% fat) for 6 weeks and injected with saline or a daily aminoimidazole carboxamide ribnucleotide (AICAR) dose of 0.5 mg/g body weight.
Chronic AMPK activation by AICAR injections resulted in a significant reduction in hepatic triglyceride accumulation in both the C and HF fed animals (C, 5.5±0.7; C+AICAR, 2.7 ±0.3; HF, 21.8±3.3; and HF+AICAR, 8.0±1.8 mg/g liver). HF feeding caused an increase in total GPAT and GPAT1 activity, which was not affected by chronic AMPK activation (GPAT1 activity vs. C, C+AICAR, 92±19%; HF, 186±43%; HF+AICAR, 234±62%). Markers of oxidative capacity, including citrate synthase activity and cytochrome c abundance, were not affected by chronic AICAR treatment. Interestingly, HF feeding caused a significant increase in long chain acyl-CoA dehydrogenase or LCAD (up 66% from C), a marker of fatty acid oxidation capacity.
These results suggest that chronic AMPK activation limits hepatic triglyceride accumulation independent of a reduction in total GPAT1 activity.
AMPK; GPAT1; SREBP-1c; mTOR; LCAD
Smoking is an important cause of morbidity and mortality worldwide. It is widely accepted as a major risk factor for metabolic and cardiovascular disease. Smoking reduces insulin sensitivity or induces insulin resistance and enhances cardiovascular risk factors such as elevated plasma triglycerides, decreases high-density lipoprotein cholesterol and causes hyperglycemia. Several studies show that smoking is associated with metabolic abnormalities and increases the risk of Metabolic Syndrome. The aim of this study was to estimate the prevalence of the metabolic syndrome in a group of light and heavy smokers, wishing to give up smoking.
In this cross-sectional study all the enrolled subjects voluntary joined the smoking cessation program held by the Respiratory Pathophysiology Unit of San Matteo Hospital, Pavia, Northern Italy.
All the subjects enrolled were former smokers from at least 10 years and had no cancer or psychiatric disorders, nor history of diabetes or CVD or coronary artery disease and were not on any medication.
The subjects smoke 32.3 ± 16.5 mean Pack Years. The prevalence of the metabolic syndrome is 52.1%: 57.3% and 44.9% for males and females respectively. Analysing the smoking habit influence on the IDF criteria for the metabolic syndrome diagnosis we found that all the variables show an increasing trend from light to heavy smokers, except for HDL cholesterol. A statistical significant correlation among Pack Years and waist circumference (R = 0.48, p < 0.0001), Systolic Blood Pressure (R = 0.18, p < 0.05), fasting plasma glucose (R = 0.19, p < 0.005) and HDL cholesterol (R = −0.26, p = 0.0005) has been observed.
Currently smoking subjects are at high risk of developing the metabolic syndrome.
Therapeutic lifestyle changes, including smoking cessation are a desirable Public health goal and should successfully be implemented in clinical practice at any age.
Metabolic syndrome; Smoking habit; Insulin resistance; Overweight; Waist circumference
Non-exercise activity thermogenesis (NEAT) is the energy expenditure due to physical activities besides active sports-like exercise and resistance training in daily life.
We studied 45 subjects (22 women and 23 men) with type 2 diabetes who did not take any hypoglycemic, anti-hypertensive, or cholesterol-lowering agents and asked them about physical activity concerned with NEAT using an original questionnaire modified from a compendium of physical activities. We studied the association of the NEAT score to body weight, waist circumference, blood pressure, glucose and lipid metabolism, and arterial stiffness.
The NEAT score was negatively correlated with serum insulin levels (r = -0.42, P < 0.05) in all subjects. The NEAT score was also negatively correlated with waist circumference (r = -0.509, P < 0.05) and positively correlated with high-density lipoprotein-cholesterol levels (r = 0.494, P < 0.05) in women, and negatively associated with serum insulin levels (r = -0.732, p < 0.005), systolic (r = -0.482, P < 0.05) and diastolic blood pressure (r = -0.538, P < 0.05) in patients with abdominal obesity. Furthermore, the NEAT score was negatively associated with pulse wave velocity (r = -0.719, P < 0.005) in smokers.
The study demonstrated that NEAT is associated with amelioration in insulin sensitivity, waist circumference, high-density lipoprotein-cholesterol, blood pressure and the marker for atherosclerosis in patients with type 2 diabetes.
Atherosclerosis; Insulin; Non-exercise activity thermogenesis; Obesity; Type 2 diabetes
The purpose of this study was to verify the effects of eight weeks of resistance training (RT) on 24 hour blood pressure (BP) in patients with and without metabolic syndrome (MetS).
Seventeen women volunteered to participate in this study, 9 with MetS (37.0 ± 8.7 yrs; body mass 77.3 ± 9.7 kg; body mass index 30.3 ± 4.2 kg · m-2) and 8 without MetS (35.1 ± 7.2 yrs; body mass 61.3 ± 8.1 kg; body mass index 24.2 ± 2.5 kg · m-2). Individuals were subjected to eight weeks (3 times/week) of whole body RT comprised of one exercise for each main muscle group with three sets of 8–12 repetitions of each subject’s maximal load . A rest interval of one minute was allowed between sets and exercises. Twenty-four hour BP was measured by ambulatory blood pressure monitoring.
Mean and diastolic night-time BP decreased (−3.9 mmHg, p = 0.04; -5.5 mmHg, p = 0.03, respectively) after eight weeks of training in MetS patients. This decrease was observed at 11:00 pm, 02:00 am (only diastolic), 07:00 am, and 6:00 pm. There was no training effect on BP in women without MetS.
Considering the elevation of BP as a contributor to the pathogenesis of MetS, and also to the increase of cardiovascular risk, this study supports RT as a non-pharmacological therapy in the management of BP control for MetS.
Resistance training; Metabolic syndrome; Blood pressure
Type 2 diabetes mellitus (T2DM) has a high prevalence and incidence around the world. The complex pathophysiology mechanism is among the barriers for diabetes treatment. Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. Linagliptin is a highly specific and potent inhibitor of DPP-4 that is currently indicated for the treatment of type 2 diabetes. Clinical studies with linagliptin demonstrated efficacy in reducing glycated hemoglobin (HbA1c) levels in type 2 diabetes patients, while maintaining a placebo-like safety and tolerability profile. Linagliptin has an interesting pharmacokinetic profile in terms of its predominantly non-renal elimination and the main implication of this characteristic is that no dose adjustment is necessary in patients with renal disease. Also, no dose adjustment is required in patients with hepatic insufficiency, as well in elderly or obese patients. This article will review the pharmacokinetic profile, efficacy data and safety aspects of linagliptin in type 2 diabetes patients.
DPP-4 inhibitor; Linagliptin; Efficacy; Safety; Renal impairment; Type 2 diabetes
Lipidomic analysis was performed to explore differences in lipid profiles between plasma from lean and obese subjects, followed by in vitro methods to examine a role for the identified lipids in endothelial cell pathophysiology.
Plasma was collected from 15 morbidly obese and 13 control subjects. Lipids were extracted from plasma and analyzed using LC/MS, and MS/MS to characterize lipid profiles and identify lipids that are elevated in obese subjects compared to lean.
Orthogonal partial least squares-discriminant analysis (OPLS-DA) modelling showed that lipid profiles were significantly different in obese subjects compared to lean. Analysis of lipids that were driving group separation in the OPLS-DA model and that were significantly elevated in the obese group led to identification of a group of ether-linked phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids of interest. Treatment of human coronary artery endothelial cells with the ether-linked phosphatidylethanolamine induced expression of cell adhesion molecules, a hallmark of endothelial cell activation. However, oxidized phosphatidylcholine products that can induce endothelial cell activation in vitro, were not significantly different between groups in vivo.
These data suggest a role for ether-linked lipids in obesity associated dyslipidemia and vascular disease.
Lipidomics; Obesity; Dyslipidemia; Endothelial cells; Oxidized phospholipids