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To analyze the effects of substituting the National Diabetes Data Group (NDDG) criteria with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) or American Diabetes Association (ADA) criteria for the diagnosis of early-onset gestational diabetes mellitus (Early-GDM) or first trimester abnormal glucose tolerance (1 t-AGT). A retrospective cohort study was conducted of 3200 women: 400 with Early-GDM, 800 with GDM, and 2000 with Non-GDM, according to the NDDG criteria. Rates of women with missed and new Early-GDM according to the IADPSG or ADA criteria were calculated. Multivariate logistic regression analysis was used to compare perinatal outcomes between groups. Using the IADPSG criteria, 61.6% of women with Early-GDM according to the NDDG were undiagnosed (Missed-Early-GDM group), and 25.9% of women with GDM and 15.7% of women with Non-GDM were diagnosed with Early-GDM (New-Early-GDM groups). Perinatal outcomes were worse in Missed-Early-GDM than in Non-GDM and better in New-Early-GDM groups than in the Early-GDM group. According to the ADA recommendations, only 11.8% of women with Early-GDM according to the NDDG criteria were diagnosed. Replacing the NDDG recommendations for the diagnosis of Early-GDM with the IADPSG or ADA criteria would mean depriving a large number of women with AGT and higher risk of adverse perinatal outcomes from early treatment and treating others with lower risk.

Aims/hypothesis Detection and management of gestational diabetes mellitus (GDM) are crucial to reduce the risk of pregnancy-related complications for both mother and child. In 2013, the WHO adopted new diagnostic criteria for GDM to improve pregnancy outcomes. However, the evidence supporting these criteria is limited. Consequently, these new criteria have not yet been endorsed in the Netherlands. The aim of this study was to determine the impact of these criteria on the number of GDM diagnoses and pregnancy outcomes. Methods Data were available from 10,642 women who underwent a 75 g OGTT because of risk factors or signs suggestive of GDM. Women were treated if diagnosed with GDM according to the WHO 1999 criteria. Data on pregnancy outcomes were obtained from extensive chart reviews from 4,431 women and were compared between women with normal glucose tolerance (NGT) and women classified into the following groups: (1) GDM according to WHO 1999 criteria; (2) GDM according to WHO 2013 criteria; (3) GDM according to WHO 2013 fasting glucose threshold, but not WHO 1999 criteria; and (4) GDM according to WHO 1999 2 h plasma glucose threshold (2HG), but not WHO 2013 criteria. Results Applying the new WHO 2013 criteria would have increased the number of diagnoses by 45% (32% vs 22%) in this population of women at higher risk for GDM. In comparison with women with NGT, women classified as having GDM based only on the WHO 2013 threshold for fasting glucose, who were not treated for GDM, were more likely to have been obese (46.1% vs 28.1%, p

Objective Growth hormone (GH) nadir (GHnadir) during oral glucose tolerance test (OGTT) is an important tool in diagnosing acromegaly, but data evaluating the need to adjust cut-offs to biological variables utilizing today's assay methods are scarce. We therefore investigated large cohorts of healthy subjects of both sexes to define normal GHnadir concentrations for a modern, sensitive, 22 kD-GH-specific assay. Design Multicenter study with prospective and retrospective cohorts (525 healthy adults: 405 females and 120 males). Methods GH concentrations were measured by the IDS-iSYS immunoassay after oral application of 75 g glucose. Results GHnadir concentrations (µg/L) were significantly higher in lean and normal weight subjects (group A) compared to overweight and obese subjects (group B); (males (M): A vs B, mean: 0.124 vs 0.065, P = 0.0317; premenopausal females without estradiol-containing OC (OC-EE) (FPRE): A vs B, mean: 0.179 vs 0.092, P POST): A vs B, mean: 0.173 vs 0.078, P nadir. However, premenopausal females on OC-EE (FPREOC) exhibited significantly higher GHnadir compared to all other groups (all P nadir in FPREOC (A vs B, mean: 0.624 vs 0.274, P = 0.1228). Conclusions BMI, sex and OC-EE intake are the major determinants for the GHnadir during OGTT in healthy adults. Using a modern sensitive GH assay, GHnadir concentrations in healthy subjects are distinctly lower than cut-offs used in previous guidelines for diagnosis and monitoring of acromegaly.

Background The use of HbA1c ≥6.5% for diagnosis of diabetes has been challenged for post-transplantation diabetes mellitus (PTDM) also known as new onset diabetes after transplantation (NODAT) due to a low sensitivity early after renal transplantation. PTDM diagnosed with an oral glucose tolerance test (OGTT) is highly predictable for long-term patient mortality. HbA1c was introduced for diagnosis based on the risk of developing diabetic retinopathy. The utility of HbA1c measures versus glucose criteria has not been widely assessed in stable transplant patients but still HbA1c is widely used in this population. The aim of the present analyses was to validate the utility of fasting plasma glucose (FPG) together with HbA1c in diagnosing PTDM in stable renal transplant recipients (RTRs). Methods OGTT’s were performed one year after transplantation in 494 consecutive RTRs without diabetes. FPG and HbA1c were obtained the same day, before starting the OGTT. Validation was performed using C-statistics and logistic regression analyses. Results PTDM was diagnosed in 51 patients (10.3%) by glucose criteria, 38 (74%) patients were diagnosed by FPG ≥7.0 mmol/L [126.1 mg/dl], and 13 (26%) only by 2-h plasma glucose. Six of the latter had HbA1c ≥6.5%. Only seven patients out of the 51 (13.7%) PTDM patients remained undiagnosed when HbA1c ≥6.5% was used together with FPG, and five of these regressed to normal after a median follow-up of 14 months. ROC curves including FPG and HbA1c versus OGTT derived criteria revealed an AUC of 0.858. Conclusions Combining standard diagnostic FPG and HbA1c criteria captured almost all patients with persistent PTDM in stable RTRs. The combined use of the criteria appears to be an applicable diagnostic strategy for PTDM without the need of an OGTT one year post-transplant. Trial registration Retrospectively registered.

Objective: To assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM. Design: A retrospective cohort study. Setting: Six secondary and tertiary delivery hospitals in Finland in 2009. Population: Pregnant women (N = 4,033) and their offspring. Methods: We used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs. Main outcome measures: GDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates. Results: Among the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring’s BWSDS and CS rate were higher than in controls. Conclusions: GDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia.

Background Oral glucose tolerance test (OGTT) is a traditional diagnostic tool for diabetes. Hemoglobin A1c (HbA1c) is an alternative method used in adults; however, its application in youths has been controversial. We evaluated the diagnostic performance of HbA1c and determined optimal cutoff points for detecting prediabetes and diabetes in youth. Methods This retrospective study included 389 obese children (217 boys, 55.8%) who had undergone simultaneous OGTT and HbA1c testing at six hospitals, Korea, between 2010 and 2016. Subjects were diagnosed with diabetes (fasting glucose ≥ 7.0 mmol/L; 2-hour glucose ≥ 11.1 mmol/L) or prediabetes (fasting glucose 5.6–6.9 mmol/L; 2-hour glucose 7.8–11.0 mmol/L). The diagnostic performance of HbA1c for prediabetes and diabetes was determined using the area under the receiver operating characteristic curve (AUC). Results At diagnosis, 197 (50.6%) subjects had normoglycemia, 121 (31.1%) had prediabetes, and 71 (18.3%) had diabetes. The kappa coefficient for agreement between OGTT and HbA1c was 0.464. The optimal HbA1c cutoff points were 5.8% (AUC, 0.795; a sensitivity of 64.1% and a specificity of 83.8%) for prediabetes and 6.2% (AUC, 0.972; a sensitivity of 91.5% and a specificity of 93.7%) for diabetes. When HbA1c (≥ 6.2%) and 2-hour glucose level were used to diagnose diabetes, 100% were detected. Conclusion Pediatric criteria for HbA1c remain unclear, therefore, we recommend the combination of fasting and 2-hour glucose levels, in addition to HbA1c, in the diagnosis of childhood prediabetes and diabetes., Graphical Abstract

Objective: To compare characteristics and outcomes of women diagnosed with gestational diabetes mellitus (GDM) by the newer one-step glucose tolerance test and those diagnosed with the traditional two-step method. Research design and methods: This was a retrospective cohort study of women with GDM who delivered in 2010–2011. Data are reported as proportion or median (interquartile range) and were compared using a Chi-square, Fisher's exact or Wilcoxon rank sum test based on data type. Results: Of 235 women with GDM, 55.7% were diagnosed using the two-step method and 44.3% with the one-step method. The groups had similar demographics and GDM risk factors. The two-step method group was diagnosed with GDM one week later [27.0 (24.0–29.0) weeks versus 26.0 (24.0–28.0 weeks); p = 0.13]. The groups had similar median weight gain per week before diagnosis. After diagnosis, women in the one-step method group had significantly higher median weight gain per week [0.67 pounds/week (0.31–1.0) versus 0.56 pounds/week (0.15–0.89); p = 0.047]. In the one-step method group more women had suspected macrosomia (11.7% versus 5.3%, p = 0.07) and more neonates had a birth weight >4000 g (13.6% versus 7.5%, p = 0.13); however, these differences were not statistically significant. Other pregnancy and neonatal complications were similar. Conclusions: Women diagnosed with the one-step method gained more weight per week after GDM diagnosis and had a non-statistically significant increased risk for suspected macrosomia. Our data suggest the one-step method identifies women with at least equally high risk as the two-step method.

Introduction: Women with previous gestational diabetes mellitus (GDM) have increased risk of developing glucose abnormality, but current diagnostic criteria are evidence-based for adverse pregnancy outcome. The aims of our study were: (i) to ascertain a frequency of early conversion of GDM into permanent glucose abnormality, (ii) to determine predictive potential of current GDM diagnostic criteria for prediction of postpartum glucose abnormality and (iii) to find optimal cut-off values of oral glucose tolerance test (oGTT) to stratify GDM population according to postpartum risk. Materials and methods: Electronic medical records of an ethnically homogenous cohort of women diagnosed and treated for GDM in a single medical centre during the period 2005–2011 who completed postpartum oGTT up to 1 year after the index delivery were retrospectively analysed (N = 305). Results: Postpartum glucose abnormality was detected in 16.7% subjects. Mid-trimester oGTT values, respective area under the curve and HbA1c were significantly associated with early postpartum glucose abnormality (P < 0.05, Mann-Whitney) and exhibited significant predictive potential for postpartum glucose abnormality risk assessment. Optimal cut-off values for discrimination of at-risk sub-population were identified using ROC analysis and their comparison with WHO and IADPSG criteria exhibited superiority of IADPSG for risk-stratification of GDM population. Conclusion: Risk-based stratification at the time of GDM diagnosis could improve efficiency of the post-gestational screening for diabetes. IADPSG criteria seem to optimally capture both perinatal and maternal metabolic risks and are therefore medically and economically justified.

Background Hospital discharge codes are often used to determine the incidence of gestational diabetes mellitus (GDM) at state and national levels. Previous studies demonstrate substantial variability in the accuracy of GDM reporting, and rarely report how the GDM was diagnosed. Our aim was to identify deliveries coded as gestational diabetes, and then to determine how the diagnosis was assigned and whether the diagnosis followed established guidelines. Methods We identified which deliveries were coded at discharge as complicated by GDM at the Brigham and Women’s Hospital in Boston, MA for the year 2010. We reviewed medical records to determine whether the codes were appropriately assigned. Results Of 7883 deliveries, coding for GDM was assigned with 98% accuracy. We identified 362 cases assigned GDM delivery codes, of which 210 (58%) had oral glucose tolerance test (OGTT) results available meeting established criteria. We determined that 126 cases (34%) received a GDM delivery code due to a clinician diagnosis documented in the medical record, without an OGTT result meeting established guidelines for GDM diagnosis. We identified only 15 cases (4%) that were coding errors. Conclusions Thirty four percent of women assigned GDM delivery codes at discharge had a medical record diagnosis of GDM but did not meet OGTT criteria for GDM by established guidelines. Although many of these patients may have met guidelines if guideline-based testing had been conducted, our findings suggest that clinician diagnosis outside of published guidelines may be common. There are many ramifications of this approach to diagnosis, including affecting population-level statistics of GDM prevalence and the potential impact on some women who may be diagnosed with GDM erroneously.

Skeletal muscle is important in insulin-stimulated glucose uptake. Sarcopenia is, therefore, a possible risk factor for insulin resistance. Currently, different diagnostic criteria for sarcopenia include low muscle mass, muscle strength, and walking speed. We assessed these muscle characteristics in relation to insulin resistance in nondiabetics. This cross-sectional study included 301 nondiabetics, mean age 65.9 years. Area under curve (AUC) calculations of insulin and glucose from a 2-h oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used as measures of insulin resistance. Muscle characteristics were relative muscle mass (total or appendicular lean mass (ALM) as percentage of body mass), absolute muscle mass (ALM/height(2) and total lean mass), handgrip strength, and walking speed. All muscle characteristics were standardized and analyzed in linear regression models, stratified by gender. For both males and females, relative muscle mass was inversely associated with AUC insulin, AUC glucose, and HOMA-IR (ALM percentage all p ≤ 0.004). Absolute muscle mass was positively associated with AUC insulin and HOMA-IR (ALM/height(2) all p < 0.001) but not with AUC glucose. Adjustments for fat mass attenuated aforementioned associations. There were no associations between handgrip strength and insulin resistance. Walking speed was inversely associated with AUC insulin in males (p = 0.032). The association between muscle characteristics and insulin resistance was strongest for relative muscle mass. Diagnostic criteria for sarcopenia relate differently to insulin resistance. The role of muscle tissue as an internal glucose-regulating organ is better reflected by relative muscle mass than by absolute muscle mass, muscle strength, or walking speed.

Background 11 patients were referred to our Molecular Genetics Department at the Royal Devon and Exeter Hospital between 2000-2012 with a physician’s diagnosis of remitting diabetes. Our aim was to identify patients with remitting diabetes whose clinical presentation is not explained by any known aetiology of diabetes. Methods We obtained longitudinal clinical data on all 11 patients from the hospital records. All patients were aged between 0.5 and 35 years at diagnosis. We applied clinical criteria derived from the literature to establish 1) definite diabetes, 2) diabetes initially severe-requiring treatment with insulin, 3) remission of diabetes, and 4) exclusion of known causes of remitting diabetes. Results 10 out of 11 patients had an alternative explanation for their remission or a clear diagnosis was not identified. We identified a single patient with idiopathic remitting diabetes using these criteria. The patient was a white Caucasian female diagnosed aged 15 with symptoms of diabetes, laboratory glucose of 21.2 mmol/L and HbA1c 134 mmol/mol. Her BMI was 23.6 kg/m2. She was treated with basal bolus insulin but discontinued two years after diagnosis due to hypoglycaemia. 13 years post diagnosis, she had a normal oral glucose tolerance test during pregnancy (fasting glucose 4.5 mmol/L, 2 hr glucose 4.8 mmol/L) and an HbA1c of 30 mmol/mol. This patient does not appear to have Type 1 or Type 2 diabetes, and furthermore does not fit into current classifications of diabetes. Conclusions Idiopathic remitting diabetes is rare but does exist. Strict clinical criteria are important to ensure patients have a robust clinical diagnosis. Identification of more patients with idiopathic remitting diabetes will enable further study of the clinical course of this syndrome. Applying these strict criteria will allow the identification of patients with remitting diabetes to assess its aetiology.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is associated with increased risks to mother and child, but globally agreed diagnostic criteria remain elusive. Identification of women with GDM is important, as treatment reduces adverse outcomes such as perinatal death, shoulder dystocia and neonatal hypoglycaemia. Recently, the UK's National Institute for Health and Care Excellence (NICE) recommended new diagnostic thresholds for GDM which are different from the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria endorsed by the WHO. The study aim was to assess neonatal and obstetric outcomes among women who would test positive for the IADPSG criteria but negative for the NICE 2015 criteria. METHODS: Data from 25,543 consecutive singleton live births (2004-2008) were obtained retrospectively from hospital records. Women were screened with a random plasma glucose (RPG; 12-16 weeks) and a 50 g glucose challenge test (GCT; 26-28 weeks). If RPG >7.0 mmol/l, GCT >7.7 mmol/l or symptoms were present, a 75 g OGTT was offered (n = 3,848). RESULTS: In this study, GDM prevalence was 4.13% (NICE 2015) and 4.62% (IADPSG). Women who 'fell through the net', testing NICE-negative but IADPSG-positive (n = 387), had a higher risk of having a large-for-gestational-age (LGA) infant (birthweight >90th percentile for gestational age; adjusted OR [95% CI] 3.12 [2.44, 3.98]), Caesarean delivery (1.44 [1.15, 1.81]) and polyhydramnios (6.90 [3.94, 12.08]) compared with women with negative screening results and no OGTT (n = 21,695). LGA risk was highest among women with fasting plasma glucose 5.1-5.5 mmol/l (n = 167): the mean birthweight was 350 g above that of the reference population and 37.7% of infants were LGA. CONCLUSIONS/INTERPRETATION: The IADPSG criteria identify women at substantial risk of complications who would not be identified by the NICE 2015 criteria.