Grandmother’s Diet Matters: Early Life Programming with Sucrose Influences Metabolic and Lipid Parameters in Second Generation of Rats

Early life exposure to certain environmental stimuli is related to the development of alternative phenotypes in mammals. A number of these phenotypes are related to an increased risk of disease later in life, creating a massive healthcare burden. With recent focus on the determination of underlying causes of common metabolic disorders, parental nutrition is of great interest, mainly due to a global shift towards a Western-type diet. Recent studies focusing on the increase of food or macronutrient intake don’t always consider the source of these nutrients as an important factor. In our study, we concentrate on the effects of high-sucrose diet, which provides carbohydrates in form of sucrose as opposed to starch in standard diet, fed in pregnancy and lactation in two subsequent generations of spontaneously hypertensive rats (SHR) and congenic SHR-Zbtb16 rats. Maternal sucrose intake increased fasting glycaemia in SHR female offspring in adulthood and increased their chow consumption in gravidity. High-sucrose diet fed to the maternal grandmother increased brown fat weight and HDL cholesterol levels in adult male offspring of both strains, i.e., the grandsons. Fasting glycaemia was however decreased only in SHR offspring. In conclusion, we show the second-generation effects of maternal exposition to a high-sucrose diet, some modulated to a certain extent by variation in the Zbtb16 gene.

Fructose consumption during pregnancy and lactation causes DNA damage and biochemical changes in female mice

The consumption of fructose during pregnancy can cause hyperglycaemia and may stimulate production of reactive oxygen species; however, there are only a few studies reporting whether fructose consumption during pregnancy causes DNA damage. Therefore, the aim of this study was to evaluate the effects of fructose consumption on genetic and biochemical parameters in Swiss mice treated during pregnancy and lactation. For this, 15 couples of 60-day-old Swiss mice were divided into three groups of five couples: negative control (water) and two fructose groups (fructose dose of 10%/l and 20%/l). During this period, we evaluated food consumption, energy efficiency and body weight. Samples of blood were collected from the females before copulation, after the 15th day of conception and on the 21st day after the lactation period, for the glycaemic and lipid profiles as well as comet assay and micronucleus (MN) test. Comet assay and MN test evaluate DNA damage and clastogenicity, respectively. In the gestation and lactation period, the two fructose doses tested showed DNA damage as observed in the comet assay, which is associated with an increase in dietary intake, body weight, lipid profile and fasting glycaemia in females. Thus, it can be suggested that the high consumption of fructose during these periods is harmful for pregnancy and lactation.

P658 Impact of hyperuricemia on left ventricular longitudinal systolic function in uncomplicated hypertensive patients

Background Hyperuricemia has been reported to accelerate the occurrence and worsening of cardiovascular disease, being a risk factor for coronary heart disease and cardiac mortality. Elevated uric acid (UA) is also associated with left ventricular (LV) hypertrophy and with LV diastolic dysfunction. The effect of hyperuricemia (HU) on LV systolic function is still unclear. Purpose Aim of our study was to evaluate the impact of elevated UA serum levels on LV systolic function, also evaluating longitudinal deformation, in a population of hypertensive patients. Methods We enrolled 160 treated hypertensive patients (M/F = 104/56, age 58.2 ± 13.3 years, blood pressure = 136.7 ± 16.8/81.3 ± 10.9 mmHg), who underwent standard echo-Doppler exam, including speckle tracking quantification of global longitudinal strain (GLS, considered in absolute value). HU was defined as UA≥7 mg/dL and the study population was divided in two groups: patients with (n = 63) and without (n = 97) HU. Exclusion criteria were coronary artery disease, overt heart failure, hemodynamically significant valve heart disease, primary cardiomyopathies, permanent atrial fibrillation and inadequate echo imaging. Results The two groups were comparable for sex prevalence, blood pressure and heart rate. Patients with HU were older and had higher body mass index (BMI) (both p < 0.0001). Prevalence of diabetes mellitus was higher in the group of patients with HU than in patients with normal UA (69% vs. 12% p < 0.0001). Fasting glycaemia was higher (p < 0.0001) and glomerular filtration rate (GFR) lower in HU hypertensives (both p < 0.0001). LV mass index (LVMi) was higher in patients with HU (p < 0.0001). Among diastolic parameters, transmitral E/A ratio (p < 0.0001) was lower, whereas E/e’ ratio (p < 0.0001), E velocity deceleration time and left atrial volume index (both p < 0.001) were higher in HU hypertensives. GLS resulted to be lower in patients with HU (20.8 ± 1.5 vs. 22.3 ± 2.2%, p < 0.0001). LV ejection fraction, despite still in normal range values, was also slightly lower in comparison with controls (60.6 ± 4.0 vs. 62.2 ± 3.9%, p < 0.01). Serum UA levels resulted to be negatively correlated with GLS (r=-0.28, p < 0.0001) (Figure), but not with ejection fraction. By a multiple linear regression analysis performed in the pooled hypertensive population, after adjusting for age, BMI, GFR, fasting glycaemia and LVMi, the association between UA levels and GLS remained significant (standardized beta coefficient =-0.25, p < 0.01), besides the significant impact of age (beta=-0.19 , p < 0.05). Conclusions In hypertensive patients with multiple cardiovascular risk factors, the presence of HU is associated with LV diastolic and systolic dysfunction. Serum UA levels and GLS resulted independently associated even after adjusting for several clinical and echo confounders. Acid uric might be considered as an independent marker of early LV dysfunction, able to identify hypertensive patients at increased risk for heart failure. Abstract P658 Figure. Relation between uric acid and GLS

P2493Change in cardiovascular health and incident type 2 diabetes and prediabetes: The Whitehall II Study

Background Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) used a single measure of CVH and none investigated the association with incident prediabetes. This study aimed to examine whether changes in CVH are associated with incident T2D and prediabetes. Methods Within the prospective Whitehall II study, CVH was examined serially every 5 years from 1991/93 until 2015/16. Subjects with 0–2, 3–4 and 5–6 ideal metrics of CVH from the American Heart Association (non-smoking, and ideal levels of body mass index, physical activity, diet, blood pressure, and total cholesterol, fasting glycaemia was not considered),were categorized as having low, moderate or high CVH. Results There were 6234 participants without prior cardiovascular disease and T2D (mean age 49.8±6.0 years, 70% male) including 5015 who were additionally free of prediabetes (49.6±6.0 years, 67% male) at baseline. Over a median follow-up of 24.8 (IQR 24.0 to 25.2) years, 895 and 1703 incident cases of T2D and prediabetes occurred respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4470 participants without CVD and T2D in the interval, and among 2798 participants additionally free of prediabetes. In multivariate analysis, compared to those with stable low CVH, risk of T2D was lower in those with initially high CVH (HR=0.23; 0.09, 0.56), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR=0.42; 0.33, 0.54), low-moderate/high (HR=0.50; 0.36, 0.69) and moderate-low (HR=0.63; 0.48, 0.83). Results were similar for prediabetes, but effect sizes were smaller. Conclusions Among participants without previous CVD, T2D or prediabetes, change in CVH was related to the risk of incident T2D and prediabetes.

Reducing the incidence of predictors of cardio-metabolic disease and dysglycaemia with lifestyle modification in at-risk persons – results of further analyses of DIABRISK-SL in those below 18 years of age

Background We have previously demonstrated in the DIABRISK-SL trial that a trimonthly pragmatic lifestyle modification (P-LSM), as compared to a 12-monthly LSM advice (C-LSM), significantly reduced the primary composite endpoint of predictors of cardio-metabolic disease (new onset type 2 diabetes (T2DM), hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia and markers of cardio-renal disease) in urban participants aged below 40 years with risk factors for T2DM. Main text We now report results of post hoc analyses for those aged below 18 (n = 1725) in three age groups, specifically of 6–10 years (P-LSM n = 77, C-LSM n = 59), 10–14 years (P-LSM n = 534, C-LSM n = 556) and 14–18 years (P-LSM n = 239, C-LSM n = 260). There was no effect of P-LSM on the primary endpoint in participants aged below 10 years. Participants aged 10–14 years in the P-LSM intervention as compared to C-LSM had a lower incidence of the primary combined endpoint (87 vs. 106 cases; incident rate ratio (IRR) = 0.85, 95% confidence intervals (CI) 0.72–1.01; P = 0.07), driven mainly by the lower incidence of new onset hypertension (24 vs. 37 cases; IRR = 0.67, 95% CI 0.49–0.91; P = 0.012). Participants aged 14–18 years in the P-LSM intervention had a lower incidence of the composite endpoint (36 vs. 54 cases; IRR = 0.73, 95% CI 0.57–0.94; P = 0.015) as well as a lower incidence of IGT (12 vs. 21 cases; IRR = 0.6, 95% CI 0.39–0.92; P = 0.02), new onset hypertension (6 vs. 15 cases; IRR = 0.43, 95% CI 0.25–0.76; P = 0.004), and new onset dysglycaemia (composite of new T2DM, IGT and impaired fasting glycaemia) (30 vs. 46 cases; IRR = 0.74, 95% CI 0.56–0.97; P = 0.03) compared to those assigned to the C-LSM intervention. Limitations of the analyses are the post hoc approach and the small number of events in each group. There were no differences in retention between the two groups. Conclusions Our results suggest that, in young South Asians aged between 10 and 18 years at risk of T2DM, a pragmatic lifestyle modification programme may reduce the incidence of predictors of T2DM and hypertension. There is a need for further studies in younger populations to evaluate the impact and feasibility of interventions to reduce the burden of T2DM and associated cardio-metabolic risk. Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0905-6

Criterion validity of metabolic and anthropometric predictors in diabetic foot syndrome

Background/Aim. The diabetic foot syndrome (DFS) appears in 15% of diabetes mellitus (DM) patients and is the most common cause of hospitalization, prolonged hospital stay and lower extremity amputation. This study assesses the discriminant validity of the indicators of glycemic control, lipoprotein status and the body mass index (BMI) in diagnosing DFS in the DM patients. Methods. A comparative observational study was conducted with the study group composed of patients diagnosed with DM and DFS and a control group, composed of healthy volunteers. Metabolic predictors measured in the study were: fasting glycaemia (FG), postprandial glycaemia (PPG), glycated hemoglobin (HbA1c), total cholesterol, total triglyceride, low density lipoprotein (LDLc) and high density lipoprotein (HDLc). The BMI was measured as an anthropometric variable. The validity criterion of both metabolic and anthropometric variables was estimated by the Receiver Operating Characteristic (ROC) procedure. Results. A total of 70 patients with DM and 60 healthy volunteers were observed. Using the ROC procedure, five significant predictors of DFS were proved. The validity criterion for HbA1c, FG, PPG, LDLc and the BMI were in the following order: 6.3%, 6.3 mmol/L, 7.1 mmol/L, 4.39 mmol/L and 25 kg/m2, respectively. Significantly larger surfaces were found under the curve for all glycometabolic variables, compared to the surface under the curve for LDLc, as well as relative to the surface under the curve for BMI. Conclusion. Preventing DFS in patients with DM has to include intensification of diet measures along with the treatment of the increased value of fasting glycaemia, postprandial glycaemia and LDLc, even when they lower compared to the current recommended values for the patients with DM. Lowering body fat in the patients with DM has to be approached in the period of their pre-obesity.