Thyroid dysfunction during gestation and gestational diabetes mellitus: a complex relationship.

PURPOSE: Gestational diabetes mellitus (GDM) and thyroid dysfunction during gestation (GTD) are the two most prevalent endocrinopathies during pregnancy. The aim of the present review is to provide an overview of the peculiar aspects of GDM and GTD, to highlight the potential interactions and clinical consequences of these two frequent clinical conditions. METHODS: A literature review regarding GDM and GTD was carried out with particular interest on meta-analyses and human studies dealing with the (i) shared risk factors between GDM and GTD, (ii) the epidemiological link between GTD and GDM, (iii) physiopathologic link between GTD and GDM, (iv) clinical consequences of GDM and GTD, and (v) post-partum implications of GDM and GTD. RESULTS: The association between GDM and GTD is common and may be explained by the insulin-resistance state due to maternal GTD, to alterations in the placentation process or to the many shared risk factors. Discrepant results of epidemiologic studies can be explained, at least in part, by the changes in diagnostic criteria and screening strategies throughout the years for both conditions. GDM and GTD impact pregnancy outcome and have post-partum long-term consequences, but more studies are needed to prove an additional adverse effect. CONCLUSIONS: Based on the epidemiological and physio-pathological link between GDM and GTD, it could be suggested that a diagnosis of GTD could lead to screen GDM and the other way round.

Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Prognosis associated with initial care of increased fasting glucose in early pregnancy: A retrospective study.

AIM: To evaluate whether the initial care of women with fasting plasma glucose (FPG) levels at 5.1-6.9mmol/L before 22 weeks of gestation (WG), termed 'early fasting hyperglycaemia', is associated with fewer adverse outcomes than no initial care. METHODS: A total of 523 women with early fasting hyperglycaemia were retrospectively selected in our department (2012-2016) and separated into two groups: (i) those who received immediate care (n=255); and (ii) those who did not (n=268), but had an oral glucose tolerance test (OGTT) at or after 22 WG, with subsequent standard care if hyperglycaemia (by WHO criteria) was present. The number of cases of large-for-gestational age (LGA) infants, shoulder dystocia and preeclampsia with initial care of early fasting hyperglycaemia were compared after propensity score modelling and accounting for covariates. RESULTS: Of the 268 women with no initial care, 134 had hyperglycaemia after 22 WG and then received care. Women who received initial care vs those who did not were more likely to be insulin-treated during pregnancy (58.0% vs 20.9%, respectively; P<0.00001), gained less gestational weight (8.6±5.4kg vs 10.8±6.1kg, respectively; P<0.00001), had a lower rate of preeclampsia [1.2% vs 2.6%, respectively; adjusted odds ratio (aOR): 0.247 (0.082-0.759), P=0.01], and similar rates of LGA infants (12.2% vs 11.9%, respectively) and shoulder dystocia (1.6% vs 1.5%, respectively). When initial FPG levels were ≥5.5mmol/L (prespecified group, n=137), there was a lower rate of LGA infants [6.7% vs 16.1%, respectively; aOR: 0.332 (0.122-0.898); P=0.03]. CONCLUSION: Treating women with early fasting hyperglycaemia, especially when FPG is ≥5.5mmol/L, may improve pregnancy outcomes, although this now needs to be confirmed by randomized clinical trials.

Is the type 2 diabetes epidemic plateauing in France? A nationwide population-based study.

AIM: Nationwide data on the evolution of diabetes incidence and prevalence are scarce in France. For this reason, our objectives were to determine type 2 diabetes prevalence and incidence rates between 2010 and 2017, stratified by gender, age and region, and to assess annual time trends over the study period in adults aged≥45 years. METHODS: Diabetes cases in the National Health Data System (SNDS), which covers the entire French population (66 million people), were identified through a validated algorithm. Gender- and age-specific prevalence and incidence rates were estimated. Negative binomial models, adjusted for gender, age and region, were used to assess annual time trends for prevalence and incidence throughout the study period. RESULTS: During 2017, 3,144,225 diabetes cases aged≥45 years were identified. Over the study period, prevalence increased slightly (men from 11.5% to 12.1%, women from 7.9% to 8.4%) whereas incidence decreased (men from 11 to 9.7, women from 7.2 to 6.2 per 1000 person-years). In only four groups did prevalence rates decrease: men aged 45-65 years; women aged 45-60 years; women in Reunion; and women in Martinique. An increasing annual time trend was observed for prevalence (men: +0.9% [95% CI: +0.7%, +1%]; women: +0.4% [95% CI: +0.2%, +0.6%]) with a decreasing annual time trend for incidence in both genders (men: -2.6% [95% CI: -3.1%, -2.0%]; women: -3.9% [95% CI: -4.5%, -3.4%]). CONCLUSION: Further efforts towards diabetes prevention are required to ensure that incidence rates in France continue to diminish, as the disorder continues to represent an important public-health burden.

Bariatric surgery and the perioperative management of type 2 diabetes: Practical guidelines.

BACKGROUND: Metabolic surgery is now considered as a therapeutic option in type 2 diabetes (T2D). However, few data are available regarding perioperative management of T2D. OBJECTIVES: To assess current practice among bariatric teams regarding perioperative management of T2D in order to propose guidelines. METHODS: A two-round Delphi method using online surveys was employed among bariatric teams experts (surgeons, diabetologists, anesthetists, nutritionists): first round, 63 questions covering 6 topics (characteristics of experts/teams, characteristics of patients, operative technique, pre/postoperative management, diabetes remission); second round, 44 items needing clarification. They were discussed within national congress of corresponding learned societies. Consensus was defined as ≥66% agreement. RESULTS: A total of 170 experts participated. Experts favored gastric bypass to achieve remission (76.7%). Screening for retinopathy, cardiac ultrasound, and reaching an HbA1c<8% are required in the pre-operative period for 67%, 75.3% and 56.7% of experts, respectively. After surgery, insulin pump should not be stopped, basal insulin should be halved, and bolus insulin should be stopped except if severe hyperglycemia. DPP-IV inhibitors and metformin are preferred after surgery. Patients should be seen by a diabetologist within one month if on oral antidiabetic agents (71.8% of experts), 2 weeks if on injectable treatments (77.1% of experts), and immediately after surgery if on insulin pump (93.5% of experts). Long-term monitoring of HbA1c is necessary even if diabetes remission (100%). CONCLUSION: Rapid postoperative modifications of blood glucose require a close monitoring and a prompt adjustment of diabetes medications.

Initially untreated fasting hyperglycaemia in early pregnancy: prognosis according to occurrence of gestational diabetes mellitus after 22 weeks' gestation: a case-control study.

AIMS: To evaluate the percentage of women with untreated fasting hyperglycaemia in early pregnancy who develop gestational diabetes mellitus after 22 weeks' gestation, the determinants of gestational diabetes development in such women and the prognosis of early fasting hyperglycaemia according to whether the women go on to develop gestational diabetes. METHODS: From a large cohort of women who delivered in our hospital between 2012 and 2016, we retrospectively selected all those who had untreated early fasting hyperglycaemia and separated them into a 'gestational diabetes' and a 'no-gestational diabetes' group according to oral glucose tolerance test results after 22 weeks' gestation. We compared the incidence of a predefined composite outcome (preeclampsia or large-for-gestational-age infant or shoulder dystocia or neonatal hypoglycaemia) in both groups. RESULTS: A total of 268 women (mean fasting plasma glucose 5.3 ± 0.3 mmol/l at a mean ± sd of 10.2 ± 4.2 weeks' gestation) were included. Gestational diabetes developed in 134 women and was independently associated with early fasting plasma glucose ≥ 5.5 mmol/l [odds ratio 3.16 (95% CI 1.57, 6.33)], age ≥ 30 years [odds ratio 2.78 (95% CI 1.46, 5.31)], preconception obesity [odds ratio 2.12 (95% CI 1.11, 4.02)], family history of diabetes [odds ratio 1.87 (95% CI 1.00, 3.50)] and current employment [odds ratio 0.46 (95% CI 0.26, 0.83)]. Despite treatment, gestational diabetes induced a significant increase in the composite outcome as compared to no gestational diabetes (odds ratio 2.16 [95% CI 1.08, 4.34]). The association disappeared after adjustment for risk factors. CONCLUSIONS: Only half of the women with early fasting hyperglycaemia and no specific care subsequently developed gestational diabetes, and these women had a poor prognosis despite gestational diabetes treatment. Poor prognosis was mostly attributable to risk factors. Our results suggest that only women with certain risk factors should be screened for early fasting hyperglycaemia.

Performance of a selective screening strategy for diagnosis of hyperglycaemia in pregnancy as defined by IADPSG/WHO criteria.

AIM: Our study evaluated the performance of a selective screening strategy for hyperglycaemia in pregnancy (HIP) based on the presence of risk factors (RFs; body mass index≥25kg/m2, age≥35years, family history of diabetes, personal history of HIP or macrosomic infant) to diagnose HIP and to predict HIP-related events. METHODS: Women with no known diabetes who had undergone complete universal screening (early, before 22weeks of gestation and, if normal, in the second part of pregnancy) at our department (2012-2016) were selected, resulting in four groups of women according to the presence of HIP and/or RFs, with a predefined composite endpoint (preeclampsia or large-for-gestational-age infant or shoulder dystocia). RESULTS: Included were 4518 women: 23.5% had HIP and 71.1% had at least one RF. The distribution among our four groups was: HIP-/RF- (n=1144); HIP-/RF+ (n=2313); HIP+/RF- (n=163); and HIP+/RF+ (n=898). HIP was more frequent when RFs were present rather than absent (33.1% vs 15.4%, respectively; P<0.001). Incidence of the composite endpoint differed significantly (P<0.0001) across groups [HIP-/RF- 6.3%; HIP-/RF+ 13.2%; HIP+/RF- 8.6%; and HIP+/RF+ 17.1% (HIP effect: P<0.05; RF effect: P<0.001; interaction HIP * RF: P=0.94)] and significantly increased with the number of RFs (no RF: 6.3%, 1 RF: 10.8%, 2 RFs: 14.7%, 3 RFs: 28.0%, 4-5 RFs: 25.0%; P<0.0001). CONCLUSION: RFs are predictive of HIP, although 15.4% of women with HIP have no RFs. Also, irrespective of HIP status, RFs are predictive of HIP-related events, suggesting that overweight/obesity, the only modifiable RFs, could be targets of interventions to improve pregnancy prognosis.

Early screening for gestational diabetes mellitus is not associated with improved pregnancy outcomes: an observational study including 9795 women.

AIMS: In addition to screening for hyperglycaemia during pregnancy after 24 weeks of gestation (WG), the current guidelines also suggest screening in early pregnancy and referring women with early gestational diabetes mellitus (eGDM) or overt diabetes (OD) for immediate care. Our aim was to evaluate this strategy. METHODS: This study evaluated, at our hospital (2012-2016), whether the incidence of a predefined composite outcome (preeclampsia, large-for-gestational-age infant, shoulder dystocia) and secondary outcomes was different when women were screened only after 22WG ('late screening only') or before 22WG and treated for eGDM or OD if present, with repeat screening after 22WG if absent ('early ± late screening'). RESULTS: Early ± late screening (n = 4605, 47.0%) increased between 2012 and 2016 (P < 0.0001) and was associated with more risk factors for GDM than late screening only. Glycaemic status differed in both groups (early ± late screening: eGDM 10.3%, GDM 12.1%, OD 0.9% vs. late screening only: GDM 16.8%, OD 1.2%; P < 0.001), with a higher rate of insulin therapy (8.9% vs. 6.0%; P < 0.001) and less gestational weight gain (11.1 ± 5.4 kg vs. 11.4 ± 5.5 kg; P = 0.013) in the early ± late screening group. Rates of those meeting the composite criterion were similar in both groups [11.6% vs. 12.0%, respectively; odds ratio (OR): 1.040, 95% confidence interval (CI): 0.920-1.176; P = 0.53] and remained comparable after adjusting for Propensity Scores (OR: 1.046, 95% CI: 0.924-1.185; P = 0.4790). Rates for secondary outcomes were also similar in both groups. CONCLUSION: While a strategy including early measurement of fasting plasma glucose during pregnancy increases the incidence and care of hyperglycaemia during pregnancy, it may not significantly improve pregnancy outcomes.

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

High Fasting Plasma Glucose during Early Pregnancy: A Review about Early Gestational Diabetes Mellitus.

Fasting plasma glucose (FPG) is nowadays routinely measured during early pregnancy to detect preexisting diabetes (FPG ≥ 7 mmol/L). This screening has concomitantly led to identify early intermediate hyperglycemia, defined as FPG in the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM). Early FPG has been associated with poor pregnancy outcomes, but the recommendation by the IADPSG to refer women with eGDM for immediate management is more pragmatic than evidence based. Although eGDM is characterized by insulin resistance and associated with classical risk factors for type 2 diabetes and incident diabetes after delivery, it is not necessarily associated with preexisting prediabetes. FPG ≥ 5.1 mmol/L in early pregnancy is actually poorly predictive of gestational diabetes mellitus diagnosed after 24 weeks of gestation. An alternative threshold should be determined but may vary according to ethnicity, gestational age, and body mass index. Finally, observational data suggest that early management of intermediate hyperglycemia may improve prognosis, through reduced gestational weight gain and potential early introduction of hypoglycemic agents. Considering all these issues, we suggest an algorithm for the management of eGDM based on early FPG levels that would be measured in case of risk factors. Nevertheless, interventional randomized trials are still missing.

Are Obese Individuals with no Feature of Metabolic Syndrome but Increased Waist Circumference Really Healthy? A Cross Sectional Study.

AIM: Patients displaying the metabolically healthy but obese phenotype have an intermediate cardiometabolic prognosis compared to normal weight healthy and metabolically unhealthy obese subjects. We aimed to evaluate the proportion of patients with a definite metabolically healthy obese phenotype and better characterize them. METHODS: Definite metabolically healthy obese phenotype was defined as having none of the International Diabetes Federation metabolic syndrome criteria, excluding waist circumference. We recruited 1 159 obese patients (body mass index 38.4±6.3 kg/m(2)) including 943 women, without known diabetes. Patients were characterized for cardiometabolic disorders. RESULTS: As the 202 (17.4%) metabolically healthy obese individuals were younger and had lower body mass indexes than the 957 metabolically unhealthy obese patients, they were matched for gender, age and body mass index with 404 metabolically unhealthy obese patients. In addition to the features of metabolic syndrome, when compared to unhealthy subjects, definite metabolically healthy obese patients were less frequently found with either homeostasis model assessment of insulin resistance index>3 (23.6 vs. 38.9%, p<0.001), or abnormal oral glucose tolerance test (13.9 vs. 33.9%, p<0.001), or HbA1c value≥5.7% (43.9 vs. 54.2%, p<0.05) or pulse pressure≥60 mmHg (11.7 vs. 64.9%, p<0.001). However, there were no significant differences in the prevalence of microalbuminuria (11.1 vs. 12.3%), cardiac autonomic dysfunction (45.5 vs. 35.3%) and fatty liver index ≥ 60 (5.6 vs. 10.2%). CONCLUSION: Our data do not support the characterization of metabolically healthy obesity, even definite, as really healthy, as many patients with this phenotype have abnormal cardiovascular markers and glucose or liver abnormalities. HbA1c measurement seems to be more sensitive than OGTT to detect dysglycemia in this population.

Fetal gender is not associated with either gestational diabetes mellitus or placental weight: A cohort study.

AIM: This study assessed whether male fetal gender increases the risk of maternal gestational diabetes mellitus (GDM) and investigated the association with placental weight. METHODS: The study included 20,149 women without pregestational diabetes who delivered singletons at our hospital between January 2002 and December 2010. There was universal screening for GDM, and all placentas were weighed at delivery. RESULTS: GDM (affecting 14.2% of women) was not associated with fetal gender (male fetuses in women without and with GDM: 51.8% vs. 51.7%, respectively; P=0.957), and remained likewise after logistic-regression analysis of risk factors for GDM (OR: 1.007, 95% CI: 0.930-1.091; P=0.858). Placental weights were 600±126g, 596±123g, 584±118g and 587±181g in women with GDM/female, GDM/male, no GDM/female and no GDM/male fetuses, respectively (GDM effect: P=0.017; gender effect: P=0.41; GDM * gender effect: P=0.16). CONCLUSION: The present results suggest that fetal gender is not associated with GDM and, while placental weights were higher in cases of GDM, there were still no gender effects.

A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin.

AIM: This study assessed whether myoinositol might be a first-line medical treatment for gestational diabetes mellitus (GDM). METHODS: For 12 months, women with GDM not controlled by diet (n=32) were prospectively treated with myoinositol 1200mg and folic acid 400µg/day, while consecutive women (n=28) with insulin-requiring GDM treated during the previous year at our centre constituted the control group. Baseline characteristics and care were similar in both groups. RESULTS: Insulin was required in eight women (25%) in the myoinositol group who, compared with the 24 who did not need insulin, were older (37±5 vs. 32±5 years, respectively; P=0.018) and had a larger percentage of high self-monitored glucose values (45±8% vs. 32±14%; P<0.0001) during the week prior to the introduction of myoinositol treatment. All of the women had similar pregnancy outcomes regardless of their GDM management, although less labour induction was required in the myoinositol group (OR: 0.22 [0.07-0.65]), which had no side effects. CONCLUSION: This pilot study suggests that myoinositol may be a safe first-line medical treatment for uncontrolled GDM.

Pregnancy adverse outcomes related to pregravid body mass index and gestational weight gain, according to the presence or not of gestational diabetes mellitus: A retrospective observational study.

AIM: This study retrospectively evaluated the complications associated with prepregnancy overweight (OW) or obesity (OB) and gestational weight gain (GWG) in women with or without universally screened and treated gestational diabetes mellitus (GDM). METHODS: A total of 15,551 non-Asian women without pregravid diabetes or hypertension who delivered singleton babies (2002-2010) were classified according to GDM (13.5%), pregestational body mass index (BMI; normal range: 18.5-24.9kg/m(2)), OW (26.2%), OB (13.9%; BMI≥30kg/m(2)) and GWG (<7kg: 32%; 7-11.5kg: 37%; 11.6-16kg: 23%;>16kg: 8%). Main outcome measures were large/small for gestational age (LGA/SGA), caesarean section, preeclampsia, preterm delivery and shoulder dystocia. RESULTS: GDM was associated with more LGA babies [Odds Ratio (OR): 2.12, 95% confidence interval (CI): 1.85-2.43], caesarean section (OR: 1.49, 95% CI: 1.34-1.65) and preeclampsia (OR: 1.59, 95% CI: 1.21-2.09). OW/OB and GWG were associated with LGA infants whatever the GDM status, and with SGA babies only in women without GDM. LGA status was independently associated with GWG in women with GDM (11.6-16kg: OR: 1.74, 95% CI: 1.49-2.03 and>16kg OR: 3.42, 95% CI: 2.83-4.13 vs 7-11.5kg) and in women without GDM (OR: 2.14, 95% CI: 1.54-2.97 or OR: 2.65, 95% CI: 1.68-4.17, respectively), and with BMI only in women without GDM (OR: 1.12, 95% CI: 1.00-1.24, per 10kg/m(2)). SGA status was independently associated with OW (OR: 0.86, 95% CI: 0.77-0.98), OB (OR: 0.84, 95% CI: 0.72-0.98) and GWG<7kg (1.14, 95% CI: 1.01-1.29) only in women without GDM. CONCLUSION: In our European cohort and considering the triumvirate of GDM, BMI and GWG, GDM was the main contributor to caesarean section and preeclampsia. OW/OB and GWG contributed to LGA and SGA infants mainly in women without GDM.

Arterial stiffness is elevated in normotensive type 2 diabetic patients with peripheral neuropathy.

BACKGROUND AND AIMS: Arterial stiffness, a measure of macrovascular damage predictive of poor cardio-vascular outcomes, is strongly related to age and hypertension (HT). In diabetic patients peripheral neuropathy (PN) has been found to be associated with increased arterial stiffness, which might be due to the concomitant presence of HT. The aim of this study was to examine in type-2 diabetic patients, the relationship between arterial stiffness and presence or absence of PN and HT separately. METHODS AND RESULTS: Arterial stiffness was measured with the gold standard carotid-femoral pulse wave velocity (PWV) in 447 type-2 diabetic subjects of whom 66% were hypertensive, 53% had PN, and 40% had both. Patients with PN were older, more often hypertensive and had higher PWV than those free of PN. Patients were separated according to the presence or absence of PN and HT. PWV values above the 90th percentile age- and blood pressure-adjusted reference range (PWV+) were different across these groups (p < 0.005) with the following respective prevalences: 27.2%, 53.4%, 33.3% and 30.6%. Only PWV+ was significantly associated with PN and hypertension in the interaction analysis. CONCLUSION: Well controlled hypertensive patients did not have elevated arterial stiffness compared to normotensive patients. This might be due to anti-hypertensive treatment although our study design does not allow us to confirm it. A strong association between PN and arterial stiffness was only present in normotensive patients, suggesting that normotensive type 2 diabetic patients with PN and elevated arterial stiffness should be carefully managed to prevent future macrovascular complications.

[Relationship between blood pressure, heart rate and cardiac autonomic dysfunction in non-diabetic obese patients]. / Relation entre pression artérielle, fréquence cardiaque et dysfonction autonome cardiaque chez les obèses non diabétiques.

RATIONALE: Some studies suggest that a high heart rate (HR) would be predictive of the incidence of an elevated blood pressure (BP). Cardiac autonomic dysfunction (CAD) affects a high proportion of obese patients. CAD could be involved in BP increase. Our aim was to examine the relationship between CAD, HR and BP in obese patients without known diabetes. PATIENTS AND METHODS: We included 428 overweight or obese patients. CAD was assessed by analyzing HR variations during three standard tests (Valsalva, deep breathing, lying-to-standing), which are mostly dependent on vagal control. An oral load in glucose was performed and the Matsuda index was calculated. RESULTS: The population was separated in 4 groups according to the grade of CAD (no or only one abnormal test, 2 or 3 abnormal tests) and HR (< or ≥ 75 bpm). Age was similar in the four groups. Systolic (P=0.05), diastolic (P<0.005) and mean BP (P<0.001) differed significantly between the 4 groups, and was the highest in the group of patients who had 2 or 3 abnormal tests and HR ≥ 75 bpm. Matsuda index differed across the groups (P=0.018) and was the lowest in this group. CONCLUSION: These data indicate that among overweight or obese patients with a defect in cardiac vagal activity BP is elevated only in those with a high heart rate, which is indicative of a more marked insulin resistance and probably an excess in sympathetic activity.