Association of parental cardiovascular risk factors with offspring type 1 diabetes mellitus insulin sensitivity

AimThis study aimed to determine whether the insulin resistance (IR) and lipid profiles in Type 1 Diabetes (T1D) offspring are associated with IR and other cardiovascular risk factors in their parents.MethodsThis study included 99 T1D patients (19.6 ± 4.0 yrs.), 85 mothers and 60 fathers. Parents' IR was assessed by HOMA-IR, and the insulin sensitivity in T1D patients was assessed by the estimated Glucose Disposal Rate (eGDR).ResultsThe eGDR in the T1D offspring was negatively related to age (p = 0.023), weight (p = 0.004), LDL (p = 0.026), and microalbuminuria (p = 0.019). Maternal Type 2 Diabetes (p < 0.001) and HOMA-IR (p = 0.029) were negatively related to eGDR in their T1D offspring. The maternal HOMA-IR and the proband's eGDR were positively (p = 0.012) and negatively (p = 0.042) associated with the birth weight of the T1D offspring, respectively. We didn't find an association with the fathers' profiles.ConclusionsIn a cohort of offspring with T1D the insulin sensitivity was related to the IR, lipid profile, and the presence of T2D only in their mothers. Precocious screening and treatment of these risk factors beyond glycemic control will benefit T1D with this background.     

Cardiovascular risk factors in overweight German children and adolescents: relation to gender, age and degree of overweight

OBJECTIVE: So far in Europe, no large studies have been published on the frequencies of the cardiovascular risk factors hypertension and dyslipidaemia in overweight children. METHODS: Diagnosis of hypertension, decreased HDL-cholesterol, increased triglycerides, total and LDL-cholesterol were documented for 1004 overweight children and adolescents (aged 4-8 years, 52% girls, BMI-SDS in median 2.43) referred to four obesity centres. Hypertension and dyslipidaemia were defined by cut off points above the 95th percentile of healthy children. Multivariate linear regression was conducted for the dependent variables systolic and diastolic blood pressure, triglycerides, HDL-, LDL-, and total cholesterol, including gender, degree of overweight (SDS-BMI) and age as independent variables. RESULTS: Thirty-seven percent of the children studied suffered from hypertension, 27% displayed increased total cholesterol, 26% increased LDL-cholesterol, 20% increased triglycerides and 18% decreased HDL-cholesterol. Seventy percent of all children had at least one unfavourable cardiovascular risk factor. Hypertension and dyslipidaemia were observed in any age group and in any degree of overweight at least twofold above the suspected rate of 5%. SDS-BMI was significantly related to blood pressure (systolic: coefficient 7.26, p < 0.001, diastolic: coefficient 3.21, p < 0.001), weakly to triglycerides (coefficient 0.12, p = 0.007), slightly negatively to HDL-cholesterol (coefficient -0.06, p = 0.001) and not related to total and LDL-cholesterol. Age was positively related to blood pressure (systolic: coefficient 2.436, p < 0.001, diastolic: coefficient 0.54, p < 0.001) and negatively to HDL cholesterol (coefficient -0.02, p < 0.001). CONCLUSION: Cardiovascular risk factors were frequently present in a large collective of overweight European children and adolescents. They occurred mostly independently of age, gender and degree of overweight. Therefore, screening for cardiovascular risk factors seems meaningful at any age and degree of overweight in childhood.     

Association of uric acid with cardiovascular risk in Brazilian children and adolescents

Background and aimHyperuricemia in adults is associated with cardiovascular risk factors. However, there is less data regarding this association in children and adolescents. Our purpose was to determine association between serum uric acid (SUA) and cardiovascular risk.Methods and resultsA fasting blood sample was collected from 1750 participants aged 6–17 years enrolled in a social project and public schools in Espírito Santo, Brazil. Internal cut-offs were generated to define high SUA (≥90th percentile of SUA concentration for sex and age group). Body mass index percentile (pBMI), body fat percentage (BFP) and muscle mass were determined by bioimpedance. Data are given as mean ± standard deviation. High SUA was associated with overweight/obesity (OR 3.7 CI 95% 2.7–5.0), high waist circumference (WC) (OR 3.9 CI 95% 2.9–5.4), low HDL (OR 2.0 CI 95% 1.5–2.8), high blood pressure (BP) (OR 1.8 CI 95% 1.1–3.2), high BFP (OR 4.1 CI 95% 2.7–6.4), metabolic syndrome (MetS) (OR 3.6 CI 95% 1.8–7.1) and insulin resistance (OR 1.7 CI 95% 1.1–2.7). Individuals in the fourth quartile of SUA, compared to those in the first quartile, showed higher age, pBMI, WC, BFP and muscle mass. Using a reference value of 5.5 mg/dL, the prevalence of hyperuricemia in the sample was 10.3% (CI 95% 8.9–11.7%).ConclusionHigher SUA values are associated with higher cardiovascular risk in childhood and adolescence. The main cardiovascular risk factors associated with hyperuricemia were overweight/obesity, high WC, dyslipidemia, high BFP, high BP, insulin resistance and MetS.     

Association between liver insulin resistance and cardiovascular risk factors

Abstract. Vangipurapu J, Stan?áková A, Kuulasmaa T, Soininen P, Kangas AJ, Ala‐Korpela M, Kuusisto J, Laakso M (University of Eastern Finland and Kuopio University Hospital, Kuopio; University of Oulu and Biocenter Oulu, Oulu, Finland). Association between liver insulin resistance and cardiovascular risk factors. J Intern Med 2012; 272: 402–408. Objectives. The objective of this study was to examine the associations between indices of liver insulin resistance (IR) and whole‐body insulin sensitivity and different cardiovascular disease (CVD) risk factors. Design and subjects. A total of 8750 nondiabetic men (age 57.2 ± 7.1 years, body mass index 26.8 ± 3.8 kg m^?2) were included in this study from the population‐based cross‐sectional Metabolic Syndrome In Men (METSIM) cohort. Liver IR index and Matsuda insulin sensitivity index (ISI) were used as markers of liver IR and whole‐body insulin sensitivity, respectively. Pearson correlation analysis was performed to examine the associations between these indices and various CVD risk factors. Results. Total cholesterol (r = ?0.088 vs. r = 0.020; P < 0.0019), high‐sensitivity C‐reactive protein (CRP) (r = 0.284 vs. r = ?0.219; P < 0.0019) and total triglycerides (r = 0.507 vs. r = ?0.477; P < 0.05) were more highly correlated with liver IR index than with Matsuda ISI. By contrast, Matsuda ISI was nominally more highly correlated with systolic and diastolic blood pressure (r = ?0.234 and r = ?0.275 vs. r = 0.202 and r = 0.239, respectively) compared to liver IR index. Furthermore, the variance explained by liver IR index was larger than that explained by Matsuda ISI for the majority of CVD risk factors measured. Conclusions. Liver IR index correlated more strongly than Matsuda ISI with levels of total cholesterol, CRP and triglycerides. Therefore, liver IR might be a significant indicator of CVD risk amongst men.     

Association of serum sialic acid with cardiovascular metabolic risk factors in Kuwaiti children and adolescents with type 1 diabetes

The aim of the present study was to investigate the relation of serum total sialic acid (TSA) concentrations with cardiovascular metabolic risk factors in Kuwaiti children and adolescents with uncomplicated type 1 diabetes. This case-control study included 150 (57 males and 93 females) type 1 diabetic children aged 6 to 18 years matched by age and sex to 150 nondiabetic children as controls. Measured variables included weight, height, systolic, diastolic blood pressure, and biochemical variables: blood glucose, glycated hemoglobin (HbA(1C)), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), apolipoproteins (apo) A1 and B, and urine microalbumin. There was no significant difference between mean serum TSA of the type 1 diabetic children (671.0 mg/L) and their controls (663.7 mg/L). In diabetic children, mean serum TSA was significantly higher in females (699.1 mg/L) than in males (625.2 mg/L) (P =.003). Significant correlations were found between serum TSA and the cardiovascular risk factors TC (P =.002), TG (P <.001), and apo B (P =.008). TSA mean level was significantly higher in diabetic children with poor glycemic control (HbA(1C) > 9.0%; P =.015), raised TC (P =.013), raised TG (P =.014), and in children with family history of cardiovascular disease (CVD; P =.02). In conclusion, the study suggests that serum TSA levels were not elevated in young type 1 diabetic children as compared with controls. The study also confirmed significant correlation of TSA concentrations with CVD risk factors TC, TG, and apo B, and as such serum TSA may be considered as a marker for CVD risk, especially in diabetic patients. A long-term prospective study is recommended to ascertain the longitudinal relationship of serum TSA with the adverse metabolic changes in type 1 diabetic children as complications prevail.     

Reduced insulin sensitivity and the presence of cardiovascular risk factors in short prepubertal children born small for gestational age (SGA)

BACKGROUND: Epidemiological studies have shown that the metabolic syndrome, a combination of type 2 diabetes mellitus, hypertension, dyslipidaemia and a high body mass index (BMI), occurs more frequently among adults who were born with a low birth weight. Because insulin is thought to play a key role in the pathogenesis of this syndrome we investigated insulin sensitivity and risk factors for cardiovascular disease in short prepubertal children born small for gestational age (SGA). PATIENTS AND METHODS: Frequently sampled intravenous glucose tolerance tests (FSIGT) were performed in 28 short prepubertal children born SGA. Short stature was defined as a height < -2SD. SGA was defined as a birth length and/or a birth weight for gestational age < -2SD. Twelve short children born appropriate for gestational age (AGA) were used as controls for the FSIGT's results only. AGA was defined as a birth weight and/or birth length for gestational age > -2SD. In short SGA children, blood pressure (BP), fasting levels of serum free fatty acids (FFA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) were measured and compared to reference values. RESULTS: Mean insulin sensitivity (Si) level in short SGA children was significantly reduced to 38% of the mean Si level measured in short AGA controls (P = 0.004). Mean acute insulin response (AIR) was significantly higher in SGA children compared to short AGA controls (P < 0.001). Differences in Si and AIR between the two groups remained significant after adjusting for age and BMI (P < 0.001 and P = 0.003, respectively). The mean (SD) systolic BP SDS was 1.3 (1,1), being significantly higher than zero. Mean fasting serum levels of FFA, TC, TG, HDL and LDL were all within the normal range. However, 6 of the 28 SGA children had serum FFA levels above the normal range. Cardiovascular risk factors could statistically be represented in two clusters. Both clusters played a significant role in the development of insulin insensitivity (1/Si). CONCLUSION: Although the metabolic syndrome has been described in adulthood, our study showed that risk factors for the development of type 2 diabetes mellitus and cardiovascular disease are already present during childhood in short prepubertal children born SGA, suggesting a pretype 2 diabetes mellitus phenotype.     

体脂分布类型和胰岛素抵抗对心血管病危险因素聚集性的 …

目的：探讨体脂分布类型和胰岛素抵抗对心血管病危险因素聚集性的影响。方法在自然人群中调查体重指数（ＢＭＩ）、腰围／臂围比值（ＷＨＲ）、血压、血胆固醇（ＴＣ）、甘油三酯（ＴＧ）、高密度脂蛋白－胆固醇（ＨＬＤ－Ｃ）、血糖（ＦＢＳ）、胰岛素（ＩＮＳ）及胰岛素敏感性指数（ＩＳＩ）。结果外周型超重组血压、ＴＧ、ＩＮＳ高于非超重组,ＨＤＬ－Ｃ、ＩＳＩ低于非超重组;而中心型超重组血压、ＩＮＳ及危险因素聚集程度高于     

Physical activity and cardiovascular disease risk factors in children and adolescents

Cardiovascular disease (CVD) is the leading cause of global mortality, and its precursors have their origin in the first decade of life. The most recognized CVD risk factors are total and central adiposity, insulin resistance, blood lipids and lipoproteins, blood pressure, inflammatory proteins, and cardiorespiratory fitness. Low physical activity is strongly associated with a higher risk of developing CVD in adults, and there is compelling evidence indicating that this is also the case in young individuals. Epidemiologic evidence indicates that a high level of physical activity, particularly vigorous physical activity, is associated with lower total and central body fat in youth. Likewise, moderate and vigorous physical activity rather than low-intensity levels seems to be independently associated with insulin resistance, blood lipids, blood pressure, inflammatory proteins, and cardiorespiratory fitness in children and adolescents. Preventive efforts should start in the first decades of life.     

Prevalence and risk factors of overweight and obesity among children and adolescents with intellectual disabilities

Recent literature reviews showed that overweight and obesity represent a major health threat in adults with intellectual disability (ID). However, the current evidence around the prevalence and risk factors associated with overweight and obesity in children and adolescents with ID remains unclear. The objective of this article was thus to review the available English‐ and French‐language studies examining the prevalence and risk factors associated with overweight and obesity in youths with ID. Ten studies providing original data on this topic were identified and included in this review. Results demonstrated that (i) overweight and obesity represent a significant secondary health problem in youths with ID; and (ii) obesity risk significantly increases with age. Considering all of the limitations of the reviewed studies (i.e. heterogeneity in sample size and in overweight and obesity classification criteria; lack of comparison group; restrictive number of risk factors examined, etc.), these findings remain preliminary and highlight the need for future research in this area.     

Hypercholesterolemia and associated cardiovascular risk factors in young children and adolescents.

OBJECTIVE: To determine the prevalence of hypercholesterolemia (HPC) and associated risk factors for cardiovascular disease, in young children and adolescents. DESIGN: Cross-sectional study, with stratification for age and gender. SETTING: Primary Care study. PATIENTS AND PARTICIPANTS: 572 young children and adolescents, five through seventeen years of age in the year 2000, with no known previous personal history of cardiovascular disease, representing the Portuguese population for age and gender. INTERVENTION: Measurement of cholesterol on an occasional whole blood sample, along with anthropometric measures, blood pressure measurement, and study of family history for cardiovascular disease factors. MEASUREMENTS AND RESULTS: 291 males and 281 females. HPC prevalence of 17.6% (male = 15.1% and female = 20.3%, ns), girls presenting with higher mean values of total cholesterol (184.75 +/- 13.27 vs. 180.27 +/- 10.44, p = 0.06). Obesity prevalence of 35.4%, and arterial hypertension of 6.6%. HPC is more common among those with positive family history for cardiovascular disease risk factors (p = 0.01). Pulse pressure is lower in the hpc group (p = 0.01). CONCLUSIONS: A hypercholesterolemia prevalence of 17.6% was found among children and adolescents, with strong association of family history for cardiovascular disease risk factors. In the light of these results, much further work will be needed to achieve reduction--or at least control--of this very important risk situation.     

Association of mood disorders with cardiovascular disease risk factors in overweight and obese youth with elevated blood pressure

The American Heart Association defines mood disorders (MDO) as a tier‐II cardiovascular disease risk factor in children. Cross‐sectional analysis of overweight/obese children referred to an obesity hypertension clinic revealed 37% had a MDO (defined by clinical diagnosis or Patient Health Questionnaire‐9/‐A score ≥10), 55% had confirmed hypertension, and 75% left ventricular hypertrophy (LVH). Children with MDOs were older, had greater measures of adiposity, and had a greater prevalence of hypertension (78%) than those without MDOs (42%; P = .04). Hypertensive children were 2.8 times more likely to have a MDO than those without (52% vs 18%; P = .02). Multivariable logistic regression revealed a statistically significant independent association of MDOs with hypertension (Odds Ratio [OR] 6.3, P = .048), but not LVH (LVMI ≥ 51 g/m^2.7; OR 1.13, P = .88). Overall, the prevalence of MDOs in this group of overweight/obese children with elevated blood pressure was well above national averages, suggesting that at‐risk youth, particularly those with confirmed hypertension, should be regularly screened for MDOs.     

Correlations between surrogate measures of insulin resistance and cardiovascular risk factors in obese and overweight patients

There are different equations to estimate insulin sensitivity by using OGTT with a reasonable approximation to whole body sensitivity obtained with the glucose clamp. Further work is needed to address their role in clinical practice as markers of the metabolic syndrome and predictors for cardiovascular disease. In the present study, we determined plasma glucose and insulin values during an OGTT test in 144 overweight and obese individuals. We assessed insulin resistance by the use of different equations and established their relationship with cardiovascular risk factors associated to the insulin resistance syndrome. Distributed the patients by quintiles of body mass index (BMI), the different surrogate measures clearly demonstrated that the more obese individuals were the most insulin resistant, a similar but not significant trend was observed related to the other cardiovascular risk factors. Efforts to use both fasting and post-load glucose and insulin concentrations to create indexes for routine use in clinical practice do not seem to be particularly useful in overweight or obese patients, as most of these patients will be insulin-resistant and insulin resistance is closely linked but not equal to the metabolic syndrome.     

Association of physical activity with insulin sensitivity in children

BACKGROUND: Physical activity (PA) has been shown to improve insulin resistance and other cardiovascular disease risk factors in normal and diabetic adults and in obese youth, but not in non-diabetic, normal-weight children. METHODS: Data from 357 non-diabetic children (10-16 y) were used to examine cross-sectional associations with PA. Insulin sensitivity was assessed with a euglycemic hyperinsulinemic clamp and expressed as M(ffm) (glucose utilization/kg of fat-free mass/min). RESULTS: Correlations were adjusted for age, sex, race and Tanner stage. PA was significantly correlated with fasting insulin and insulin sensitivity (r=-0.12, P=0.03 and r=0.13, P=0.001, respectively), more strongly in children with above-median systolic blood pressure (r=-0.17, P=0.03 and r=0.35, P=0.0001, respectively). Further adjustment for body mass index, body fat percentage, waist circumference or lipids did not alter these observations. CONCLUSIONS: Physical activity is correlated with lower fasting insulin and greater insulin sensitivity in childhood. These results are consistent with the hypothesis that increasing physical activity among youth may reduce the incidence of type 2 diabetes in children and adolescents.     

Obesity and cardiovascular risk in children and adolescents

The global prevalence of overweight and obesity in children and adolescents has increased substantially over the past several decades. These trends are also visible in developing economies like India. Childhood obesity impacts all the major organ systems of the body and is well known to result in significant morbidity and mortality. Obesity in childhood and adolescence is associated with established risk factors for cardiovascular diseases and accelerated atherosclerotic processes, including elevated blood pressure (BP), atherogenic dyslipidemia, atherosclerosis, metabolic syndrome, type II diabetes mellitus, cardiac structural and functional changes and obstructive sleep apnea. Probable mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system and altered vascular function. Adiposity promotes cardiovascular risk clustering during childhood and adolescence. Insulin resistance has a strong association with childhood obesity. A variety of proinflammatory mediators that are associated with cardiometabolic dysfunction are also known to be influenced by obesity levels. Obesity in early life promotes atherosclerotic disease in vascular structures such as the aorta and the coronary arteries. Childhood and adolescent adiposity has strong influences on the structure and function of the heart, predominantly of the left ventricle. Obesity compromises pulmonary function and increases the risk of sleep-disordered breathing and obstructive sleep apnea. Neglecting childhood and adolescent obesity will compromise the cardiovascular health of the pediatric population and is likely to result in a serious public health crisis in future.     

Association of acylated and nonacylated ghrelin with insulin sensitivity in overweight and obese postmenopausal women

OBJECTIVE: Ghrelin [acylated (AG) and nonacylated (NAG)] has been shown to play a pivotal role in the regulation of food intake and insulin sensitivity. It is presently unclear whether variation in insulin sensitivity is related to AG and NAG levels in obese individuals. To address this issue, we determined whether insulin-sensitive overweight or obese (ISO) and insulin-resistant overweight or obese (IRO) individuals display different total ghrelin (TotG), AG, and NAG profiles during a euglycemic/hyperinsulinemic clamp (EHC). DESIGN: Eighty-nine nondiabetic overweight and obese postmenopausal women underwent EHC to evaluate insulin sensitivity. Body composition and blood lipid profiles were assessed. Subjects within the highest tertile of insulin sensitivity were described as ISO (n = 31), whereas those within the lowest tertile of insulin sensitivity were considered as IRO (n = 29). Plasma TotG, AG, and NAG profiles were assessed by RIA at 0, 60, 160, 170, and 180 min during the EHC. RESULTS: TotG and NAG levels were significantly decreased for ISO and IRO individuals during the EHC, whereas only ISO subjects displayed a significant reduction of AG concentrations (P < 0.05). AG area under the curve value and the ratio of AG/NAG (fasting and area under the curve) were significantly decreased in ISO individuals. Furthermore, maximal reduction of TotG and AG concentrations was greater in ISO compared with IRO individuals (P < 0.05). Insulin sensitivity was significantly correlated with maximal reduction of TotG (r = 0.36; P < 0.01) and AG (r = 0.36; P < 0.05) concentrations. CONCLUSION: The dysregulation of ghrelin secretion profiles during EHC is associated with insulin resistance. AG may contribute to the variation of insulin sensitivity in overweight or obese postmenopausal women.