Alessandra Bertolotto

n-3 Fatty Acids in the Treatment of Diabetic Patients: Biological rationale and clinical data

The current interest for the use of n-3 (polyunsaturated) fatty acids in vascular disease can be originally tracked to observations in Greenland Inuits (Eskimos), revealing a lower prevalence of coronary heart disease (CHD) in these populations compared with Scandinavian control subjects (1–4). In a series of pioneering studies, Dyerberg and Bang (5,6) originally showed that Inuits had an attenuated platelet reactivity and a prolonged bleeding time compared with Scandinavian control subjects. This was attributed to the Eskimo diet, with an extremely high content of fish or of fish-derived products (such as seal), abundant in n-3 fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (7). In other populations with a high consumption of fish, such as the Japanese (8,9) and the Alaskans (10), a similar inverse correlation between fish consumption and mortality from CHD has been subsequently found. However, in Western populations with a generally low intake of n-3 fatty acids, both protective effects (11–16) and no effects (17–20) of n-3 fatty acids on CHD have been reported. There are good explanations for the lack of uniformity in the epidemiological data, including the difficulty in maintaining constant feeding habits in a population during long observational studies and the influence of other dietary principles, including the simultaneous ingestion of saturated or other unsaturated fatty acids. Overall, the bulk of epidemiological data suggests the existence of favorable associations between fish consumption and mortality from CHD (21–24), as reflected in a recent health statement from the American Heart Association (25). In addition, a host of in vitro and in vivo studies have provided possible biological explanations for the epidemiological observations. Such studies have demonstrated that 1 ) diets rich in n-3 fatty acids partially replace n-6 with n-3 fatty acids in …

Compound Heterozygosity for a Structural Apolipoprotein A-I Variant, Apo A-I(L141R)Pisa, and an Apolipoprotein A-I Null Allele in Patients With Absence of HDL Cholesterol, Corneal Opacifications, and Coronary Heart Disease

BACKGROUND The concentration of HDL cholesterol is inversely correlated with the risk of coronary heart disease (CHD). Some rare mutations in the apolipoprotein (apo) A-I gene are associated with low levels of HDL cholesterol. Their association with cardiovascular risk is controversial. METHODS AND RESULTS We studied the molecular defects underlying corneal opacities and absence of HDL cholesterol in three brothers and a sister. In a family study, the importance of these defects for lipid metabolism and manifestation of coronary heart disease was investigated. The frequency of these apo A-I defects was assessed by genotype and phenotype analysis of 477 DNA- and plasma samples, respectively, from the population. The four patients were compound heterozygotes for a null allele and a missense mutation in the apo A-I gene that leads to a leucine-->arginine substitution at residue 141 [apo A-I(L141R)Pisa]. Heterozygotes for either the null allele or the structural variant had half-normal concentrations of HDL cholesterol and apo A-I compared with unaffected family members. Apo A-I(L141R)Pisa was detected in one more unrelated subject. Coronary angiography of the four compound heterozygotes revealed the presence of CHD in all male patients, whose ages ranged between 45 and 52 years. They presented with additional risk factors, including elevated LDL cholesterol levels, obesity, and arterial hypertension. Despite complete HDL deficiency and hypercholesterolemia, CHD was absent in the 51-year-old premenopausal sister. CONCLUSIONS Apo A-I deficiency may lead to premature atherosclerosis if present in conjunction with additional cardiovascular risk factors.

DALI: Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: an European multicentre, randomised trial - study protocol

BackgroundGestational diabetes mellitus (GDM) is an increasing problem world-wide. Lifestyle interventions and/or vitamin D supplementation might help prevent GDM in some women.Methods/designPregnant women at risk of GDM (BMI≥29 (kg/m2)) from 9 European countries will be invited to participate and consent obtained before 19+6 weeks of gestation. After giving informed consent, women without GDM will be included (based on IADPSG criteria: fasting glucose<5.1mmol; 1 hour glucose <10.0 mmol; 2 hour glucose <8.5 mmol) and randomized to one of the 8 intervention arms using a 2×(2×2) factorial design: (1) healthy eating (HE), 2) physical activity (PA), 3) HE+PA, 4) control, 5) HE+PA+vitamin D, 6) HE+PA+placebo, 7) vitamin D alone, 8) placebo alone), pre-stratified for each site. In total, 880 women will be included with 110 women allocated to each arm. Between entry and 35 weeks of gestation, women allocated to a lifestyle intervention will receive 5 face-to-face, and 4 telephone coaching sessions, based on the principles of motivational interviewing. The lifestyle intervention includes a discussion about the risks of GDM, a weight gain target <5kg and either 7 healthy eating ‘messages’ and/or 5 physical activity ‘messages’ depending on randomization. Fidelity is monitored by the use of a personal digital assistance (PDA) system. Participants randomized to the vitamin D intervention receive either 1600 IU vitamin D or placebo for daily intake until delivery. Data is collected at baseline measurement, at 24–28 weeks, 35–37 weeks of gestation and after delivery. Primary outcome measures are gestational weight gain, fasting glucose and insulin sensitivity, with a range of obstetric secondary outcome measures including birth weight.DiscussionDALI is a unique Europe-wide randomised controlled trial, which will gain insight into preventive measures against the development of GDM in overweight and obese women.Trial registrationISRCTN70595832

Effect of physical activity and/or healthy eating on GDM risk: The DALI Lifestyle Study

Context Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results. Objective The aim of the present study was to compare the effectiveness of 3 lifestyle interventions [healthy eating (HE), physical activity (PA), and both HE and PA (HE+PA)] with usual care (UC) in reducing GDM risk. Design The present study was a multicenter randomized controlled trial conducted from 2012 to 2014 [the DALI (vitamin D and lifestyle intervention for GDM prevention) lifestyle study]. Setting The study occurred at antenatal clinics across 11 centers in 9 European countries. Patients Consecutive pregnant women at <20 weeks of gestation with a body mass index (BMI) of ≥29 kg/m2 and without GDM using the International Association of Diabetes and Pregnancy Study Group criteria (n = 436). For the intervention, women were randomized, stratified by site, to UC, HE, PA, or HE+PA. The women received 5 face-to-face and ≤4 telephone coaching sessions using the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. The coaches received standardized training and an intervention toolkit tailored to their culture and language. Main Outcome Measures The endpoints were the GWG at 35 to 37 weeks and the fasting glucose and insulin sensitivity [homeostasis model assessment insulin resistance (HOMA-IR)] at 24 to 28 weeks. Results We randomized 108 women to HE+PA, 113 to HE, 110 to PA, and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially less GWG than did the controls (UC) by 35 to 37 weeks (-2.02; 95% confidence interval, -3.58 to -0.46 kg). Despite this reduction, no improvements were seen in fasting or postload glucose levels, insulin concentrations, or HOMA-IR. The birthweights and large and small for gestational age rates were similar. Conclusions The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycemia. Thus, lifestyle changes alone are unlikely to prevent GDM among women with a BMI of ≥29 kg/m2.

Early Subclinical Atherosclerosis in Women With Previous Gestational Diabetes Mellitus

To determine if women with previous gestational diabetes mellitus (pGDM), a population at high risk for type 2 diabetes and metabolic syndrome (1), have signs of subclinical atherosclerosis, we measured carotid intimal-medial thickness (IMT) and multiple cardiovascular risk factors in 28 women with and 24 without pGDM (control group) 2 years after delivery. A 75-g 2-h oral glucose tolerance test was performed for assessment of glucose tolerance, area under the glucose curve (AUCgluc), insulin sensitivity index, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, and fibrinogen. Family history, anthropometric parameters, and blood pressure were recorded. IMT was measured at four segments of …

METABOLIC EFFECTS OF THREE NEW LOW-DOSE PILLS : A SIX-MONTH EXPERIENCE

We evaluated the effects on glucose and lipid metabolism in 57 healthy volunteers randomly assigned to one of three low-dose oral contraceptives: two monophasic (desogestrel + ethinylestradiol, EE, and cyproterone acetate + EE) and one triphasic (gestodene + EE) contraceptives. Glucose and insulin responses during OGTT were slightly affected by the cyproterone pill. The insulin area/glucose area ratio and HbA1c level were unchanged in all women. No preparation affected total and LDL-cholesterol levels. Triglycerides rose in all groups, while HDL-CH did only in women taking the two monophasic pills. The three low-dose pills assessed in this study have negligible effects on glucose and lipid metabolism.

Continuous subcutaneous insulin infusion and multiple dose insulin injections in Type 1 diabetic pregnant women: a case-control study

The aim of this study was to evaluate the effects of continuous subcutaneous insulin infusion (CSII) on glycemic control and pregnancy outcomes in Type 1 diabetic pregnant women. We retrospectively evaluated 42 subjects, 20 treated with CSII and 22 with multiple dose insulin injections (MDI). The two groups were comparable for age, pre-pregnancy BMI, and primiparous rate, whereas women in the CSII group showed a tendency toward a longer diabetes duration (p = 0.06). Pre-pregnancy diabetic retinopathy and/or nephropathy were present in nine women of CSII and three of MDI. In all women metabolic control improved during pregnancy, without differences between the two groups and at the end of gestation HbA1c was 6.3 ± 0.6 in CSII and 6.1 ± 1.1% in MDI. Moreover, there were no differences in weight gain, whereas insulin requirement resulted significantly (p = 0.009) lower in CSII than in MDI. We recorded only one severe hypoglycaemic episode in both groups. No cases of deteriorations of the chronic diabetic complications were observed. The delivery occurred at 36.4 ± 2.2 weeks; birth weight, the rate of large for gestational age, and the parameters of foetal morbidity were similar in both groups. In conclusions, CSII and MDI are both effective in improving maternal glucose control and have both similar pregnancy outcomes.

IADPSG and WHO 2013 Gestational Diabetes Mellitus Criteria Identify Obese Women With Marked Insulin Resistance in Early Pregnancy

Implementation of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization 2013 (WHO 2013) recommendations leads to an increased prevalence of gestational diabetes mellitus (GDM) due to more stringent criteria and early screening of women at high risk for diabetes in pregnancy (DIP) (1,2). IADPSG members now recommend that their GDM criteria should not be used in early pregnancy but have not provided alternative criteria (3). We have compared the characteristics of overweight/obese women early in pregnancy, with and without GDM using the new criteria, to assess whether those testing positive are metabolically distinct. Pregnant women with a BMI ≥29.0 kg/m2 underwent a 75-g oral glucose tolerance test in early pregnancy as part of enrollment into the DALI (Vitamin D And Lifestyle Intervention for GDM prevention) pilot and lifestyle Pan-European multicenter trials (4). GDM and DIP were diagnosed using WHO 2013 criteria. A high rate of GDM (237/1,035 or 22.9%: DIP 0.5%; total hyperglycemia in early pregnancy 23.4%) was found at a …

Effect of plasma metformin concentrations on serum lipid levels in type II diabetic patients

SummaryIn this study we evaluated the relationships between plasma metformin levels, measured by reversed-phase high-performance liquid chromatography, and serum lipid levels in 20 metformintreated, type II diabetic patients. Mean fasting plasma metformin concentration was 490 ± 188 ng/ml. No correlation was found between daily dose of drug and lipid parameters. A significant correlation emerged between circulating metformin concentration and serum triglycerides (r=−0.574, p<0.01), HDL-cholesterol (r=0.583, p<0.01) and HDL2-cholesterol (r=0.670, p<0.05). Multiple linear regression analysis showed that the correlation between plasma metformin concentration and serum triglycerides still remained significant after correction for other clinical and metabolic parameters. Total cholesterol and HDL3-cholesterol were not correlated with metformin concentrations. These results demonstrate the clinical usefulness of measuring plasma metforminc concentrations and indicate that some effects of metformin on lipid metabolism depend on the drug plasma levels.

Selective screening for GDM in Italy: application and effectiveness of National Guidelines

Abstract In September 2011 the Italian Public Health Authority established selective screening for GDM to be performed based on the presence of risk factors. In a cohort of 2552 Caucasian pregnant women we evaluated to which extent the new national guidelines (NGL) are correctly applied; moreover we estimated the prevalence of GDM assessed by NGL. Our data show that the NGL are still properly implemented since the screening test was performed in nearly the totality of the women at 24th and 28th week of gestation. GDM prevalence is 10.9%, 25% greater as compared to the one determined with the old criteria 10 years ago.