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.

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.

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.

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.

New evidence of broader diets for archaic Homo populations in the northwestern Mediterranean.

Investigating diet breadth is critical for understanding how archaic Homo populations, including Neanderthals, competed for seasonally scarce resources. The current consensus in Western Europe is that ungulates formed the bulk of the human diet during the Lower and Middle Paleolithic, while small fast prey taxa were virtually ignored. Here, we present a multisite taphonomic study of leporid assemblages from Southern France that supports frequent exploitation of small fast game during marine isotope stages 11 to 3. Along with recent evidence from Iberia, our results indicate that the consumption of small fast game was more common prior to the Upper Paleolithic than previously thought and that archaic hominins from the northwestern Mediterranean had broader diets than those from adjacent regions. Although likely of secondary importance relative to ungulates, the frequent exploitation of leporids documented here implies that human diet breadths were substantially more variable within Europe than assumed by current evolutionary models.

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.

Obstructive sleep apnoea syndrome in patients living with diabetes: Which patients should be screened?

AIM: Because type 2 diabetes (T2D) is related to obesity, it is often associated with obstructive sleep apnoea syndrome (OSAS), although OSAS is also frequently diagnosed in patients with type 1 diabetes (T1D) and may promote gestational diabetes. Thus, this systematic review of the scientific evidence aimed to evaluate the epidemiological association between OSAS and all forms of diabetes, the current understanding of the pathophysiological mechanisms behind these associations, the expected benefits and limitations of OSAS treatment in patients with diabetes and, finally, to propose which patients require screening for OSAS. METHODS: A panel comprising French expert endocrinologists and pneumologists was convened. Two of these experts made a search of the relevant literature for each subpart of the present report; all panel experts then critically reviewed the entire report separately as well as collectively. RESULTS: There is little evidence to support the notion that OSAS treatment improves glycated haemoglobin, although it may improve nighttime blood glucose control and insulin sensitivity. However, there is robust evidence that OSAS treatment lowers 24-h blood pressure. CONCLUSION: The high prevalence of OSAS in patients with T1D and T2D justifies screening for the syndrome, which should be based on clinical symptoms, as the benefits of OSAS treatment are mainly improvement of symptoms related to sleep apnoea. There are also several clinical situations wherein screening for OSAS seems justified in patients with diabetes even when they have no symptoms, particularly to optimalize control of blood pressure in cases of resistant hypertension and microvascular complications.

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.

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.

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.

Which oral antidiabetic drug to combine with metformin to minimize the risk of hypoglycemia when initiating basal insulin?: A randomized controlled trial of a DPP4 inhibitor versus insulin secretagogues.

We conducted a pilot study to evaluate two therapeutic strategies at the time of insulin initiation in type 2 diabetic patients insufficiently controlled with metformin+insulin-secretagogues (IS, sulfonylureas or glinides). Patients were randomized to remain under the same dual therapy or to receive metformin+DPP4 inhibitors while starting insulin. Similar glycemic control was achieved in both groups. However less hypoglycemia was observed with DPP4 inhibitors despite higher doses of insulin.