SEVERE REFRACTORY HYPOTHYROIDISM IN A 48-YEAR-OLD FEMALE: ROLE OF LOW-DOSE THYROXINE ABSORPTION TEST IN ESTABLISHING DIAGNOSIS OF NONCOMPLIANCE.

A 48-year-old female presented with severe chronic hypothyroidism despite progressively increasing doses of levothyroxine. Poor adherence was suspected based on previous laboratory investigations. A low dose thyroxine absorption test using 400 µg of levothyroxine taken orally was performed. FT4 increased by 4.7 pmol/L at 3 hours and 6.6 pmol/L at 5 hours, following ingestion, effectively ruling out malabsorption. Her cardiac hemodynamic profile, measured noninvasively, also improved following levothyroxine intake, further supporting our diagnosis. Poor adherence was successfully managed by implementing twice weekly visits by a registered nurse and an improvement in both thyroid function tests and cardiac parameters was seen at the one-month follow-up visit. We suggest using a lower dose thyroxine absorption test, owing to its efficacy in establishing diagnosis and a safer alternative compared to higher doses in particular in high-risk cardiac patients.

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.

Congestive heart failure caused by silent ischemia and silent myocardial infarction : Diagnostic challenge in type 2 diabetes.

In asymptomatic patients with type 2 diabetes (T2D), the prevalence of silent myocardial infarction on routine electrocardiograms is about 4% while for silent myocardial ischemia it is 20-30%. Some studies showed that silent myocardial infarction is associated with an increased risk of incident heart failure (HF), whereas no prospective study has ever reported such a risk in patients with silent myocardial ischemia. In patients with HF, however, previously unrecognized coronary artery disease (CAD) often seems to be involved. Brain natriuretic peptide (BNP) and N­terminal pro-BNP (NT-proBNP) levels represent first-line diagnostic tools for patients with suspected HF and might also serve as biomarkers for silent CAD. Echocardiography provides a detailed report of cardiac alterations that includes changes suggestive of ischemia, heart failure, and left ventricular dysfunction in addition to strong prognostic indices. Diabetic patients with silent myocardial infarction or silent myocardial ischemia should be screened for asymptomatic changes in left ventricular function or structure. In patients with silent CAD, all risk factors need to be better controlled and the choice of antihyperglycemic agents adjusted. In patients with congestive HF and no obvious cause of HF, invasive coronary angiography (or noninvasive computed tomography angiography) should be performed to detect CAD, since the finding of CAD may involve revascularization and requires additional treatments including antiplatelet agents and statins. Future research is needed to examine the cost effectiveness of screening for silent myocardial ischemia as part of HF risk assessment, and to identify preventive therapies to lower the risk of HF among patients with silent myocardial infarction.

Metabolic syndrome in adolescents: definition based on regression of IDF adult cut-off points.

OBJECTIVES: The objective of this study was to derive a sex- and age-specific definition of the metabolic syndrome (MetS) and its abnormalities for adolescents. STUDY DESIGN: This is a cross-sectional study. METHODS: A total of 1100 adolescent students, aged 12-18 y, were randomly selected from schools and classrooms in the city of Constantine, Algeria; all had anthropometric measurements taken, and 989 had blood tests. Gender-specific growth curves for components of the MetS were derived, using the LMS (lambda-mu-sigma) method, and the percentiles corresponding to the thresholds of the MetS components proposed for adults by the International Diabetes Federation (IDF) were identified. RESULTS: The prevalence of the MetS using this new definition was 4.3% for boys and 3.7% for girls (P = 0.64). Overall, a high waist circumference was the most frequent of the syndrome components, but the frequency was much higher in girls than that in boys, 33.6% and 6.9%, respectively. In contrast, a high systolic blood pressure was seen in 26.8% of the boys and only 11.4% of the girls. The prevalence of the MetS was higher among adolescents with a body mass index (BMI) ≥95th percentile of the study population, 28.8%, against 9.8% in adolescents with a BMI between the 95th and 85th percentile and 1.8% in those with a BMI <85th percentile (P < 0.0001). CONCLUSION: MetS during adolescence requires more studies to establish a consensus definition. For clinical practice, we propose a simplified definition for boys and girls based on regression of IDF adult cut-off points. This definition should be tested in further studies with other adolescent populations.

Improving postpartum glucose screening after gestational diabetes mellitus: a cohort study to evaluate the multicentre IMPACT initiative.

AIMS: To evaluate a mobilization campaign, the IMPACT initiative, which included multidisciplinary meetings, provision of information and a systematic prescription of an oral glucose tolerance test to improve the rate of glucose screening in women with gestational diabetes mellitus in the four largest maternity units in our area, starting in March 2011. METHODS: We retrospectively compared the level of self-reported screening during the first 6 months postpartum of women who gave birth after having been diagnosed with gestational diabetes before (January 2009 to December 2010) and after the IMPACT campaign (April 2011 to February 2012). RESULTS: We included 961 women (589 in the period before and 372 in the period after the campaign was initiated) with a mean ± SD age of 33.2 ± 5.3 years and BMI of 27.8 ± 5.3 kg/m². Multivariate analysis, stratified using a propensity score in order to limit bias caused by imbalance between both periods, showed that the postpartum screening rate was higher after the campaign began (48.9 vs 33.3%, odds ratio 1.7, 95% CI 1.1-2.5; P = 0.019) and higher in women who received insulin treatment during pregnancy (odds ratio 2.3, 95% CI 1.5-3.6; P < 0.001), consumed fruit and vegetables daily (odds ratio 1.6, 95% CI 1.1-2.4; P = 0.035) and did not smoke (smoking vs non-smoking: odds ratio 0.3, 95% CI 0.1-0.7; P = 0.01). There was no interaction between the campaign effect and these particular conditions. The proportion of oral glucose tolerance tests performed in women who underwent screening increased from 6.3 to 33.0%. CONCLUSIONS: The IMPACT campaign increased postpartum screening, and the use the oral glucose tolerance test in particular. The effect of this initiative might be reinforced in women who are non-daily consumers of fruit and vegetables, smokers and those who do not receive insulin treatment during pregnancy.

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.

Insulin- and glucagon-like peptide-1-induced changes in heart rate and vagosympathetic activity: why they matter.

Heart rate (HR) predicts cardiovascular morbidity and mortality in individuals either with or without diabetes. In type 2 diabetic patients, cardiac autonomic neuropathy is a risk marker for cardiac morbidity and mortality. A major pathogenic potential may be attributed to vagal depression and sympathetic predominance. In this issue of Diabetologia, Berkelaar et al (DOI: 10.1007/s00125-013-2848-6 ) examined the effects of euglycaemic, and hyperglycaemic clamp with the addition of glucagon-like-peptide-1 (GLP-1) and arginine, on cardiac vagal control in a large number of healthy subjects. After adjustments for age, BMI and insulin sensitivity, insulin associations with HR remained partially intact while those with vagal control disappeared. This suggested that BMI and insulin sensitivity, but not insulin levels, were the main drivers of cardiac vagal control. GLP-1 infusion during hyperglycaemia increased HR and BP and produced a statistically non-significant decrease in measures of cardiac vagal control compared with values before any manipulation of insulin levels. This commentary summarises how, and to what extent, insulin and GLP-1 affect autonomic nervous system activity, HR and BP. More information is needed on the mechanisms through which acute administration of, and long-term treatment with, GLP-1 may affect haemodynamics and autonomic activity in diabetic and obese patients, since this may influence cardiovascular outcomes.

Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial.

AIMS/HYPOTHESIS: The aim was to evaluate the efficacy and safety of transcutaneous frequency-modulated electromagnetic neural stimulation (frequency rhythmic electrical modulation system, FREMS) as a treatment for symptomatic peripheral neuropathy in patients with diabetes mellitus. METHODS: This was a double-blind, randomised, multicentre, parallel-group study of three series, each of ten treatment sessions of FREMS or placebo administered within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The primary endpoint was the change in nerve conduction velocity (NCV) of deep peroneal, tibial and sural nerves. Secondary endpoints included the effects of treatment on pain, tactile, thermal and vibration sensations. Patients eligible to participate were aged 18-75 years with diabetes for ≥ 1 year, HbA(1c) <11.0% (97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities (i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural nerve, but with an evocable potential and measurable NCV of the sural nerve), a Michigan Diabetes Neuropathy Score ≥ 7 and on a stable dose of medications for diabetic neuropathy in the month prior to enrolment. Data were collected in an outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1 ratio) according to a sequence generated by a computer random number generator, without block or stratification factors. Investigators digitised patients' date of birth and site number into an interactive voice recording system to obtain the assigned treatment. Participants, investigators conducting the trial, or people assessing the outcomes were blinded to group assignment. RESULTS: Patients (n = 110) with symptomatic neuropathy were randomised to FREMS (n = 54) or placebo (n = 56). In the intention-to-treat population (50 FREMS, 51 placebo), changes in NCV of the three examined nerves were not different between FREMS and placebo (deep peroneal [means ± SE]: 0.74 ± 0.71 vs 0.06 ± 1.38 m/s; tibial: 2.08 ± 0.84 vs 0.61 ± 0.43 m/s; and sural: 0.80 ± 1.08 vs -0.91 ± 1.13 m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in day and night pain as measured by a visual analogue scale immediately after each treatment session, although this beneficial effect was no longer measurable 3 months after treatment. Compared with the placebo group, in the FREMS group the cold sensation threshold was significantly improved, while non-significant differences were observed in the vibration and warm sensation thresholds. No relevant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS proved to be a safe treatment for symptomatic diabetic neuropathy, with immediate, although transient, reduction in pain, and no effect on NCV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01628627. FUNDING: The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy), lately Lorenz Lifetech (Ozzano dell'Emilia, Italy).

A simple new non-invasive sweat indicator test for the diagnosis of diabetic neuropathy.

A simple non-invasive indicator test (Neuropad(®)) has been developed for the assessment of sweating and, hence, cholinergic innervation in the diabetic foot. The present review summarizes current knowledge on this diagnostic test. The diagnostic ability of this test is based on a colour change from blue to pink at 10 min, with excellent reproducibility, which lends itself to patient self-examination. It has a high sensitivity (65.1-100%) and negative predictive value (63-100%), with moderate specificity (32-78.5%) and positive predictive value (23.3-93.2%) for the diagnosis of diabetic peripheral neuropathy. It also has moderate to high sensitivity (59.1-89%) and negative predictive value (64.7-91%), but low to moderate specificity (27-78%) and positive predictive value (24-48.6%) for the diagnosis of diabetic cardiac autonomic neuropathy. There are some data to suggest that Neuropad can detect early diabetic neuropathy, but this needs further evaluation. It remains to be established whether this test can predict foot ulceration and amputation, thereby contributing to the identification of high-risk patients.

Decreased stroke volume−brachial pulse pressure ratio in patients with type 2 diabetes over 50 years: the role of peripheral neuropathy.

BACKGROUND AND AIMS: To document the stroke volume to pulse pressure ratio (SV/PP, an index of total arterial compliance) and its correlates in patients with type 2 diabetes (T2DM) aged over 50 years whose peripheral neuropathy and silent myocardial ischemic (SMI) status were known. METHODS AND RESULTS: A total of 360 patients with T2DM aged ≥ 50 years, without cardiac history or symptom, left ventricular systolic dysfunction, dilatation and hypokinesia, were retrospectively enrolled. The SV/PP was calculated from echocardiographic left ventricular measurements and brachial blood pressure at rest. Peripheral neuropathy was defined as the presence of any two or more of the following: neuropathic symptoms, decreased distal sensation, or decreased or absent ankle reflexes. SMI was defined as an abnormal stress myocardial scintigraphy and/or stress echocardiography. A low SV/PP ratio (<0.53 ml/m²/mmHg, first tertile) was associated with age, creatinine clearance, 24 h urinary albumin excretion rate, peripheral neuropathy, hypertension, serum total cholesterol and triglycerides levels (p < 0.05-0.0001). In multivariate analysis, age (OR 1.1 [1.0-1.2], p < 0.01), triglycerides (OR 1.5 [1.2-2.0], p = 0.01) and peripheral neuropathy (OR 2.2 [1.2-3.9], p = 0.009) were independently associated with a low SV/PP. The patients with peripheral neuropathy had lower SV (p < 0.01) and higher PP (p < 0.05) than those without, and only lower SV after adjustment for age and nephropathy. Similar results were obtained in the patients with and without SMI. CONCLUSION: Peripheral neuropathy was independently associated with decreased SV/PP, mainly through decreased SV, in patients with T2DM over 50 years.

The report of male gender and retinopathy status improves the current consensus guidelines for the screening of myocardial ischemia in asymptomatic type 2 diabetic patients.

BACKGROUND AND AIMS: American Diabetes Association (ADA), French-speaking Societies for diabetes & cardiology (ALFEDIAM-SFC) and Cardiac Radionuclide Imaging (CRI) have proposed guidelines for the screening of silent myocardial ischemia (SMI). The aim of the study was to evaluate their diagnostic values and how to improve them. METHODS AND RESULTS: 731 consecutive type 2 diabetic patients with ≥1 additional risk factor were screened between 1992 and 2006 for SMI by stress myocardial scintigraphy and for silent coronary artery disease (CAD) by coronary angiography. A total of 215 (29.4%) patients had SMI, and 79 of them had CAD. ADA (Odds Ratio 1.7 [95% Confidence Interval: 1.2-2.5]; p < 0.05), ALFEDIAM-SFC (OR 1.5 [1.0-2.5], p < 0.05) and CRI criteria (OR 2.0 [1.4-2.8], p < 0.01) predicted SMI. Considering the presence of male gender and retinopathy added to the prediction of SMI allowed by ADA criteria (c statistic: area under the curve AROC 0.651 [0.605-0.697] versus 0.582 [0.534-0.630]), p < 0.01 and ALFEDIAM-SFC criteria (AROC 0.672 [0.620-0.719] versus 0.620 [0.571-0.670], p < 0.05). CRI prediction of SMI was improved by considering the presence of macroproteinuria and retinopathy (AROC 0.621 [0.575-0.667] versus 0.594 [0.548-0.641], p < 0.01). Severe retinopathy (OR 3.4 [1.2-9.4], p < 0.05), smoking habits (OR 2.1 [1.1-4.2], p < 0.05) and triglyceride levels (OR 1.3 [1.0-1.6], p < 0.05) were independent predictors of CAD in the patients with SMI. CONCLUSION: Current guidelines criteria are able to predict SMI but prediction may be improved by considering male gender and the presence of retinopathy. CAD is more frequent in the patients with SMI who are current smokers, have severe retinopathy and higher triglyceride levels.

1-h post-load plasma glucose for detecting early stages of prediabetes.

Prediabetes is a very prevalent condition associated with an increased risk of developing diabetes and/or other chronic complications, in particular cardiovascular disorders. Early detection is therefore mandatory since therapeutic interventions may limit the development of these complications. Diagnosis of prediabetes is currently based on glycemic criteria (fasting plasma glucose (PG), and/or glycemia at 120 min during a 75 g oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c). Accumulating longitudinal evidence suggests that a 1-hour PG ≥155 mg/dl (8.6 mmol/l) during the OGTT is an earlier marker of prediabetes than fasting PG, 2-h post-load PG, or HbA1c. There is substantial evidence demonstrating that the 1-h post-load PG is a more sensitive predictor of type 2 diabetes, cardiovascular disease, microangiopathy and mortality compared with conventional glucose criteria. The aim of this review is to highlight the paramount importance of detecting prediabetes early in its pathophysiological course. Accordingly, as recommended by an international panel in a recent petition, 1-h post-load PG could replace current criteria for diagnosing early stages of "prediabetes" before prediabetes evolves as conventionally defined.

Management strategies for gastrointestinal, erectile, bladder, and sudomotor dysfunction in patients with diabetes.

There are substantial advances in understanding disordered gastrointestinal autonomic dysfunction in diabetes. It occurs frequently. The underlying pathogenesis is complex involving defects in multiple interacting cell types of the myenteric plexus as well. These defects may be irreversible or reversible. Gastrointestinal symptoms represent a major and generally underestimated source of morbidity for escalating health care costs in diabetes. Acute changes in glycaemia are both determinants and consequences of altered gastrointestinal motility. 35-90% of diabetic men have moderate-to-severe erectile dysfunction (ED). ED shares common risk factors with CVD. Diagnosis is based on medical/sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to patient's complaints and risk factors. Treatment is based on PDE5-inhibitors (PDE5-I). Other explorations may be useful in patients who do not respond to PDE5-I. Patients at high cardiovascular risk should be stabilized by their cardiologists before sexual activity is considered or ED treatment is recommended. Estimates on bladder dysfunction prevalence are 43-87% of type 1 and 25% of type 2 diabetic patients, respectively. Common symptoms include dysuria, frequency, urgency, nocturia and incomplete bladder emptying. Diagnosis should use validated questionnaire for lower urinary tract symptoms. The type of bladder dysfunction is readily characterized with complete urodynamic testing. Sudomotor dysfunction is a cause of dry skin and is associated with foot ulcerations. Sudomotor function can be assessed by thermoregulatory sweat testing, quantitative sudomotor axon reflex test, sympathetic skin response, quantitative direct/indirect axon reflex testing and the indicator plaster.

What would be the outcome if the American Diabetes Association recommendations of 2010 had been followed in our practice in 1998-2006?

AIMS: In 2010, the American Diabetes Association has published recommendations on the population to be screened for dysglycaemia; the diagnostic criteria for intermediate hyperglycaemia and diabetes using oral glucose tolerance testing and HbA(1c); and the patients eligible for treatment with metformin. We aimed to evaluate the consequences of screening with oral glucose tolerance test or HbA(1c) in an at-risk population. METHODS: Among 1177 overweight or obese consecutive adults without known diabetes who were referred to our department for weight management, we selected 1157 individuals (83% female; 80% European) fulfilling the American Diabetes Association 2010 criteria for dysglycaemia screening. RESULTS: Mean age was 41.2 ± 13 years, BMI 37.0 ± 7.2 kg/m(2), fasting plasma glucose 4.9 ± 0.8 mmol/l and HbA(1c) (turbidimetric immunoassay) 5.7 ± 0.7% (39 mmol/mol). Based on oral glucose tolerance test and HbA(1c), respectively, 76 (6.6%) and 113 (9.8%) patients had diabetes, including 34 sharing both criteria; 307 (26.5%) and 478 (41.3%) had intermediate hyperglycaemia; and 130 (11.2%) and 255 (22.0%) would be treated with metformin. The sensitivity/specificity of HbA(1c) ≥ 6.5% (48 mmol/mol) for the diagnosis of diabetes according to the oral glucose tolerance test were 44.7/92.7%. Diabetes risk scores and UK Prospective Diabetes Study cardiovascular risk score were the highest in the 130 patients having both an abnormal oral glucose tolerance test and HbA(1c) ≥ 5.7%. CONCLUSIONS: In a population at risk for diabetes, the HbA(1c) strategy could lead to diagnosing more cases of dysglycaemia and to treating more patients with metformin than the oral glucose tolerance test strategy. The consistency of either diagnostic criteria was low. The patients with the highest a priori risk of diabetes and cardiovascular disease were those fulfilling both oral glucose tolerance test and HbA(1c) criteria.

Influence of blood glucose on heart rate and cardiac autonomic function. The DESIR study.

OBJECTIVES: To evaluate in a general population, the relationships between dysglycaemia, insulin resistance and metabolic variables, and heart rate, heart rate recovery and heart rate variability. METHODS: Four hundred and forty-seven participants in the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) study were classified according to glycaemic status over the preceding 9 years. All were free of self-reported cardiac antecedents and were not taking drugs which alter heart rate. During five consecutive periods: rest, deep breathing, recovery, rest and lying to standing, heart rate and heart rate varability were evaluated and compared by ANCOVA and trend tests across glycaemic classes. Spearman correlation coefficients quantified the relations between cardio-metabolic risk factors, heart rate and heart rate varability. RESULTS: Heart rate differed between glycaemic groups, except during deep breathing. Between rest and deep-breathing periods, patients with diabetes had a lower increase in heart rate than others (P(trend) < 0.01); between deep breathing and recovery, the heart rate of patients with diabetes continued to increase, for others, heart rate decreased (P(trend) < 0.009). Heart rate was correlated with capillary glucose and triglycerides during the five test periods. Heart rate variability differed according to glycaemic status, especially during the recovery period. After age, sex and BMI adjustment, heart rate variability was correlated with triglycerides at two test periods. Change in heart rate between recovery and deep breathing was negatively correlated with heart rate variability at rest, (r=-0.113, P < 0.05): lower resting heart rate variability was associated with heart rate acceleration. CONCLUSIONS: Heart rate, but not heart rate variability, was associated with glycaemic status and capillary glucose. After deep breathing, heart rate recovery was altered in patients with known diabetes and was associated with reduced heart rate variability. Being overweight was a major correlate of heart rate variability.

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.

Association between cardiac autonomic neuropathy and hypertension and its potential influence on diabetic complications.

AIMS: To examine the association between cardiac autonomic neuropathy and hypertension and the role of this association in diabetic complications. METHODS: We included 310 patients, 138 with Type 1 and 172 with Type 2 diabetes, 62 of them with hypertension. Cardiac autonomic neuropathy was assessed by analysing heart rate variations during three standard tests (deep breathing, lying to standing and Valsalva) and looking for postural hypotension. RESULTS: Cardiac autonomic neuropathy was present in 123 patients and 39 also had hypertension. The prevalence of a cardiac autonomic neuropathy/hypertension association was higher in Type 2 patients (P < 0.002). The prevalence of hypertension increased with the severity of cardiac autonomic neuropathy. In multiple logistic regression analysis, cardiac autonomic neuropathy was an independent risk factor for hypertension [odds ratio 2.86 (1.54-5.32); P < 0.001]. Only confirmed or severe cardiac autonomic neuropathy (two or more abnormal function tests, respectively) were independent risk factors for hypertension (P < 0.005 and < 0.0001). Cardiac autonomic neuropathy was found in most of the patients with macrovascular complications, retinopathy or nephropathy, but a large majority of the patients with these complications exhibited the cardiac autonomic neuropathy/hypertension profile. This profile was more prevalent among the patients with coronary or peripheral artery disease or antecedent stroke than among those free of these complications (P < 0.001). In logistic regression analyses, the cardiac autonomic neuropathy/hypertension profile associated significantly with macro- and microvascular complications. CONCLUSIONS: These data are strongly in favour of the role of cardiac autonomic neuropathy in hypertension in diabetic patients. The association of the cardiac autonomic neuropathy/hypertension profile with vascular complications is consistent with a deleterious effect on vascular hemodynamics and structure, additional to the effects of hypertension.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

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.

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.