Longitudinal changes in glucose during pregnancy in women with gestational diabetes risk factors.

AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as ß (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum. CONCLUSIONS/INTERPRETATION: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy.

Three-year clinical outcome in all-comers with "silent" diabetes, prediabetes, or normoglycemia, treated with contemporary coronary drug-eluting stents: From the BIO-RESORT Silent Diabetes study.

BACKGROUND: Patients with coronary disease may have unknown diabetes or prediabetes. We evaluated 3-year outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES) in patients with silent diabetes, prediabetes, and normoglycemia. METHODS: All BIO-RESORT trial (NCT01674803) participants without known diabetes, enrolled at our center, were invited for oral glucose tolerance testing (OGTT) and measurements of fasting plasma glucose and glycated hemoglobin (HbA1c). RESULTS: OGTT detected silent diabetes in 68 (6.9%), prediabetes in 132 (13.4%), and normoglycemia in 788 (79.8%) of all 988 study participants. Follow-up was available in 986 (99.8%) patients. The main endpoint target vessel failure (TVF: cardiac death, target vessel-related myocardial infarction [MI], or target vessel revascularization) differed between groups (14.8, 9.9, and 5.6%; p = .002), driven by MI during the first 48 hr and by cardiac death (p < .001; p = .026). Between 48 hr and 3-years, there was no significant between-group difference in TVF, target vessel MI, and target vessel revascularization. Multivariable analysis demonstrated that silent diabetes was independently associated with TVF (adjusted HR: 2.52, 95%-CI: 1.26-5.03). An alternative diagnostic approach-HbA1c and fasting plasma glucose-detected silent diabetes and prediabetes in 33 (3.3%) and 217 (22.0%) patients, and normoglycemia in 738 (74.7%); TVF rates were 12.1, 7.9, and 6.0% (p = .23). CONCLUSION: In patients without known diabetes, abnormal glucose metabolism by OGTT was independently associated with higher 3-year TVF rates after PCI with contemporary DES. This difference was driven by periprocedural MI and cardiac death. After the first 48 hr, the rates of TVF, target vessel MI, and target vessel revascularization were low and did not differ significantly between metabolic groups.

Discriminatory ability of anthropometric measurements of central fat distribution for prediction of post-prandial hyperglycaemia in patients with normal fasting glucose: the DICAMANO Study.

BACKGROUND AND AIMS: Obesity is associated with impaired glucose tolerance which is a risk factor for cardiovascular risk. However, the oral glucose tolerance test (OGTT) is not usually performed in patients with normal fasting glycaemia, thus offering false reassurance to patients with overweight or obesity who may have post-prandial hyperglycaemia. As an alternative to resource demanding OGTTs, we aimed to examine the predictive value of anthropometric measures of total and central fat distribution for post-prandial hyperglycaemia in patients with overweight and obesity with normal fasting glycaemia enrolled in the DICAMANO study. METHODS: We studied 447 subjects with overweight/obesity with a fasting glucose value ≤ 5.5 mmol l-1 (99 mg dl-1) and BMI ≥ 25 kg/m2 who underwent a 75-g OGTT. Post-prandial hyperglycaemia was defined as a glucose level ≥ 7.8 mmol l-1 (140 mg dl-1) 2-h after the OGTT. The anthropometric measurements included body mass index, body adiposity index, waist circumference, neck circumference, waist-to-hip ratio and waist-to-height ratio. RESULTS: The prevalence of post-prandial hyperglycaemia was 26%. Mean 1-h OGTT glucose levels, insulin resistance and beta cell dysfunction was higher in those subjects in the highest tertile for each anthropometric measurement, irrespective of fasting glucose level. Central fat depot anthropometric measurements were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. After multivariable-adjustment for fasting plasma glucose level, smoking, and physical activity level, the odds ratio (95% confidence intervals) for the presence of post-prandial hyperglycaemia for neck circumference, waist circumference and waist-to-height ratio were 3.3 (1.4, 7.7), 2.4 (1.4, 4.4) and 2.5 (1.4, 4.5), respectively. CONCLUSIONS: In this large and comprehensively phenotyped cohort, one in four subjects had post-prandial hyperglycaemia despite normal fasting glycaemia. Anthropometric indices of central fat distribution were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. These results support the association between central adiposity and glucose derangements and demonstrate the clinical usefulness of anthropometric measurements as screening tools for the selection of patients who are most likely to benefit from an OGTT. Trial registration ClinicalTrials.gov Identifier: NCT03506581. Registered 24 April 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03506581.

Seasonality, temperature and pregnancy oral glucose tolerance test results in Australia.

BACKGROUND: The oral glucose-tolerance test (OGTT) is currently the standard method for diagnosis of gestational diabetes (GDM). We conducted a post hoc analysis using the Australian Hyperglycemia and Adverse Pregnancy Outcome (HAPO) data to determine seasonal variations in OGTT results, the consequent prevalence of GDM, and association with select perinatal parameters. METHOD: Women enrolled in the Australian HAPO study sites (Brisbane and Newcastle) from 2001 to 2006 were included if OGTT results between 24 to 32 weeks gestation were available (n = 2120). Fasting plasma glucose, 1-h plasma glucose, 2-h plasma glucose, HbA1c, HOMA-IR, and umbilical cord C-peptide and glucose values were categorized by season and correlated to monthly temperature records from the Australian Bureau of Meteorology for Brisbane and Newcastle. GDM was defined post hoc using the IADPSG/WHO criteria. RESULTS: Small but significant (p <  0.01 on ANOVA) elevations in fasting glucose (+ 0.12 mM), HbA1c (+ 0.09%), and HOMA-IR (+ 0.88 units) were observed during the winter months. Conversely, higher 1-h (+ 0.19 mM) and 2-h (+ 0.33 mM) post-load glucose values (both p <  0.01) were observed during the summer months. The correlations between fasting glucose, 1-h glucose, 2-h glucose, and HbA1c with average monthly temperatures confirmed this trend, with positive Pearson's correlations between 1-h and 2-h glucose with increasing average monthly temperatures, and negative correlations with fasting glucose and HbA1c. Further, umbilical cord C-peptide and glucose displayed negative Pearson's correlation with average monthly temperature, aligned with trends seen in the fasting plasma glucose. Overall prevalence of GDM did not display significant seasonal variations due to the opposing trends seen in the fasting versus 1-h and 2-h post-load values. CONCLUSION: A significant winter increase was observed for fasting plasma glucose, HbA1c, and HOMA-IR, which contrasted with changes in 1-h and 2-h post-load venous plasma glucose values. Interestingly, umbilical cord C-peptide and glucose displayed similar trends to that of the fasting plasma glucose. While overall prevalence of GDM did not vary significantly by seasons, this study illustrates that seasonality is indeed an additional factor when interpreting OGTT results for the diagnosis of GDM and provides new direction for future research into the seasonal adjustment of OGTT results.

Maternal vitamin D and neonatal anthropometrics and markers of neonatal glycaemia: Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks' gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks' gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

Screening for type 2 diabetes and prediabetes in obese youth: evaluating alternate markers of glycemia - 1,5-anhydroglucitol, fructosamine, and glycated albumin.

Hemoglobin A1c (HbA1c) is increasingly performed over the oral glucose tolerance test (OGTT) as the initial screening test for type 2 diabetes in youth. However, the optimal strategy for identifying type 2 diabetes in youth remains controversial. Alternate glycemic markers have been proposed as potentially useful tools for diabetes screening. We examined the relationships among fructosamine (FA), glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG) with traditional screening tests, HbA1c and OGTT. Youth 10-18 yrs, BMI ≥85th‰, and HbA1c <7.5% had a single visit with measurement of HbA1c, 1,5-AG, FA, GA, and a standard OGTT. Distributions of FA, GA, and 1,5-AG by HbA1c and 2-hour glucose (2hG) categories were compared. Receiver operating characteristic (ROC)-curves were generated to determine the cut points at which alternate markers maximized sensitivity and specificity for predicting prediabetes and diabetes. One hundred and seventeen, 62% female, 59% Hispanic, 22% White, 17% black, median 14.1 yr, and body mass index (BMI) z-score 2.3 participated. Median values of each alternate marker differed significantly between prediabetes and diabetes HbA1c and 2hG categories (p < 0.017). Only GA medians differed (p = 0.006) between normal and prediabetes HbA1c. Area under the receiver operating characteristic curves (ROC-AUCs) for alternate markers as predictors of prediabetes (0.5-0.66) were low; however, alternate marker ROC-AUCs for identifying diabetes (0.82-0.98) were excellent. Although the alternate markers were poor predictors of prediabetes, they all performed well predicting diabetes by 2hG and HbA1c. Whereas the usefulness of these markers for identifying prediabetes is limited, they may be useful in certain scenarios as second line screening tools for diabetes in overweight/obese youth.

Early glucose abnormalities revealed by continuous glucose monitoring associate with lung function decline in cystic fibrosis: A five-year prospective study.

BACKGROUND: Cystic fibrosis related diabetes (CFRD) is commonly associated with declining lung function and nutritional status. We aimed to evaluate the pulmonary impact of early glucose abnormalities by using 2-h standard oral glucose tolerance testing (OGTT) and continuous glucose monitoring (CGM) in people with cystic fibrosis (PwCF). METHODS: PwCF aged ≥10 years old without known CFRD were included in a five-year prospective multicentre study. Annual evaluation of nutritional status, lung function, OGTT and CGM was set up. Associations between annual rate changes (Δ) in lung function, ΔFEV1 (forced expiratory volume in 1 s) percentage predicted (pp) and ΔFVC (forced vital capacity) pp., and annual rate changes in OGTT or CGM variables were estimated with a mixed model with a random effect for subject. RESULTS: From 2009 to 2016, 112 PwCF (age: 21 ± 11 years, BMI (body mass index) z-score: -0.55 ± 1.09, FEV1pp: 77 ± 24 %, 2-h OGTT glucose: 122 ± 44 mg/dL, AUC (area under curve) >140 mg/dL: 1 mg/dL/day (0.2, 3.0) were included. A total of 428 OGTTs and 480 CGMs were collected. The participants presented annual decline of FVCpp and FEV1pp at -1.0 % per year (-1.6, -0.4), p < 0.001 and - 1.9 % per year (-2.5, -1.3), p < 0.001 respectively without change in BMI z-score during the study. Variation of two-hour OGTT glucose was not associated with declining lung function, as measured by ΔFEV1pp (p = 0.94) and ΔFVCpp (p = 0.90). Among CGM variables, only increase in AUC >140 mg/dL between two annual visits was associated with a decrease in ΔFVCpp (p < 0.05) and ΔFEV1pp (p < 0.05). CONCLUSIONS: This prospective study supports the fact that early glucose abnormalities revealed by CGM predict pulmonary function decline in PwCF, while 2-h standard OGTT glucose is not associated with pulmonary impairment.

Oral glucose tolerance testing at 1 h and 2 h: relationship with glucose and cardiometabolic parameters and agreement for pre-diabetes diagnosis in patients with morbid obesity.

BACKGROUND: One hour plasma glucose concentration (1hPG) during an oral glucose tolerance test (OGTT) may be an alternative to 2-h plasma glucose concentration (2hPG) in the identification of individuals at increased risk of hyperglycaemia, although its role is not fully understood. AIM: We aim to investigate the relationship of these measures with other glucose parameters, as well as their relationship with cardiometabolic risk markers and the level of agreement for prediabetes mellitus diagnosis, in a sample of patients with morbid obesity. METHODS: We retrospectively evaluated 656 patients with morbid obesity without diagnosed diabetes. To define prediabetes with 2hPG, 2022 American Diabetes Association guidelines criteria were used, while for 1hPG, glucose ≥ 155 mg/dL was considered. Cohen's Kappa coefficient was used to assess the agreement between both measures of prediabetes mellitus diagnosis. RESULTS: A Cohen's Kappa coefficient of 0.405 (p < 0.001) was obtained. The 1hPG were positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR) (ρ = 0.281, p < 0.001), fasting plasma glucose (FPG) (ρ = 0.581, p < 0.001), glycated haemoglobin (Hb1AC) (ρ = 0.347, p < 0.001) and were negatively correlated with homeostatic model assessment for cell-ß function (HOMA-ß) (ρ = -0.092, p = 0.018). 2hPG were also correlated with the same parameters, except for HOMA-ß. CONCLUSION: A fair agreement between 1 and 2hPG was verified. 1hPG criteria may be a useful indicator of ß-cell dysfunction and insulin resistance in patients with morbid obesity without diabetes diagnosis.

The Relationship Between Continuous Glucose Monitoring and OGTT in Youth and Young Adults With Cystic Fibrosis.

CONTEXT: Early glucose abnormalities in people with cystic fibrosis (PwCF) are commonly detected by continuous glucose monitoring (CGM). Relationships between these CGM abnormalities and oral glucose tolerance testing (OGTT) in PwCF have not been fully characterized. OBJECTIVE: This work aimed to determine the relationship between CGM and common OGTT-derived estimates of ß-cell function, including C-peptide index and oral disposition index (oDI) and to explore whether CGM can be used to screen for OGTT-defined prediabetes and cystic fibrosis-related diabetes (CFRD). METHODS: PwCF not on insulin and healthy controls aged 6 to 25 years were enrolled in a prospective study collecting OGTT and CGM. A subset underwent frequently sampled OGTTs (fsOGTT) with 7-point glucose, insulin, and C-peptide measurements. Pearson correlation coefficient was used to test the association between select CGM and fsOGTT measures. Receiver operating curve (ROC) analysis was applied to CGM variables to determine the cutoff optimizing sensitivity and specificity for detecting prediabetes and CFRD. RESULTS: A total of 120 participants (controls = 35, CF = 85), including 69 with fsOGTTs, were included. CGM coefficient of variation correlated inversely with C-peptide index (Cpeptide30-Cpeptide0/Glucose30-Glucose0) (r = -0.45, P < .001) and oDIcpeptide (C-peptide index)(1/cpep0) (r = -0.48, P < .0001). In PwCF, CGM variables had ROC - areas under the curve ranging from 0.43 to 0.57 for prediabetes and 0.47 to 0.6 for CFRD. CONCLUSION: Greater glycemic variability on CGM correlated with reduced ß-cell function. However, CGM performed poorly at discriminating individuals with and without OGTT-defined CFRD and prediabetes. Prospective studies are now needed to determine how well the different tests predict clinically relevant nonglycemic outcomes in PwCF.

Glycemia and ß-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis.

Background: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear. Methods: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), insulin resistance (HOMA2 IR and IS(OGTT Cpep)), and ß-cell function (C-peptide oral disposition index, oDIcoeo), were compared before and after ETI. Results: Participants were a median (IQR) of 20.4 (14.1, 28.6) years old, 75 % male. Follow-up occurred 10.5 (10.0, 12.3) months after ETI initiation. BMI z-score increased from 0.3 (-0.3, 0.8) to 0.8 (0.4, 1.5), p = 0.013 between visits. No significant differences were observed in glucose tolerance, glucose area under the curve, nor fsOGTT glucose concentrations before and after ETI. Median (IQR) C-peptide index increased from 5.7 (4.1, 8.3) to 8.8 (5.5, 10.8) p = 0.013 and HOMA2 IR increased (p < 0.001), while oDIcoeo was unchanged (p = 0.67). HbA1c decreased from 5.5 % (5.5, 5.8) to 5.4 % (5.2, 5.6) (p = 0.003) while CGM variables did not change. Conclusions: BMI z-score and measures of both insulin resistance and insulin secretion increased within the first year of ETI initiation. ß-cell function adjusted for insulin sensitivity (oDIcoeo) did not change.

Cystic fibrosis-related diabetes: Prevalence, screening, and diagnosis.

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). Prevalence of CFRD increases with age and is greater with severe mutations. Other risk factors associated with CFRD are female sex, pancreatic insufficiency, liver disease, need for gastrostomy tube feedings, history of bronchopulmonary aspergillosis, and poor pulmonary function. CFRD is related to worse clinical outcomes and increased mortality. Early diagnosis and treatment have been shown to improve clinical outcomes. Screening for CFRD is recommended with an annual oral glucose tolerance test (OGTT) starting at age 10 years. Diagnosis of CFRD is made by standard American Diabetes Association (ADA) criteria during baseline health. CFRD can also be diagnosed in individuals with CF during acute illness, while on enteral feeds, and after transplant. In this review we will discuss the epidemiology of CFRD and provide an overview of the advantages and pitfalls of current screening and diagnostic tests for CFRD.

Measuring visfatin levels in saliva: an alternative approach to gestational diabetes screening.

OBJECTIVE: Oral glucose tolerance testing (OGTT) is the current recommended approach for the diagnosis of gestational diabetes mellitus (GDM). Visfatin is a type of novel adipokine of interest that mostly participates in glucose metabolism and inflammatory processes. We aim to identify a screening technique for GDM using salivary visfatin levels and to establish this technique's value as a screening method compared to OGTT. METHODS: This is a cross-sectional case-control study. The cohort was formed from the saliva samples of pregnant patients in their 24th through 28th weeks of gestation. Patients were divided into two groups depending on their GDM status. OGTT and visfatin test results were compared and subjected to further analysis to establish a cutoff value for visfatin testing. RESULTS: ELISA results indicated a significant difference between patients with GDM compared to patients without GDM; the values were 18.89 ± 9.59 and 12.44 ± 8.75, respectively (p: 0.007). A cutoff value of 10.5 ng/mL can be used to detect GDM with 78% sensitivity and 51% specificity. CONCLUSION: Salivary visfatin levels were significantly higher in patients with GDM. The existence of a differential in the concentration of visfatin in saliva can be utilized to develop a new screening method for GDM.

Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis.

Oral glucose tolerance testing (OGTT) is the primary method to screen for and diagnose cystic fibrosis-related diabetes (CFRD). Diagnostic thresholds as currently defined are based on microvascular complications seen in type 2 diabetes. Abnormal glucose tolerance (AGT) refers to OGTT glucose elevations outside the normal range and encompasses both impaired and indeterminate glucose tolerance. Current guidelines define impaired glucose tolerance (IGT) as a 2-hour glucose of 140-199 mg/dL (7.8-11 mmol/L) and indeterminate glucose tolerance (INDET) as any mid-OGTT glucose ≥ 200 mg/dL (11.1 mmol/L) with a normal fasting and 2 h glucose. There is growing evidence that AGT also has associations with CF-centered outcomes including pulmonary decline, hospitalizations, and weight loss. Here we aim to review the historical emergence of glucose tolerance testing, review relevance to risk stratification for CFRD, discuss alternate cutoffs for identifying AGT earlier, and highlight the need for larger, future studies to inform our understanding of the implications of IGT and INDET on CF health.

Reproducibility of a prediabetes classification in a contemporary population.

AIMS: To assess whether meeting both fasting plasma glucose (FPG) and HbA1c criteria for prediabetes in people at high risk indicates with near certainty the presence of dysglycemia on repeat testing. METHODS: Observational study using data from Vitamin D and Type 2 Diabetes (D2d) study. HbA1c, FPG were measured at screening visit 1; FPG, HbA1c and 2 h plasma glucose (2hPG) measured at screening visit 2 (a median of 21 days later); participants classified as having normal glucose regulation (all 3 tests in normal range), prediabetes or diabetes (at least 1 of 3 tests in diabetes range). A predictive model was developed to estimate the probability of confirming dysglycemia and for detecting diabetes at screening visit 2 based on values of FPG and HbA1c at screening visit 1. RESULTS: Of 1271 participants who met both FPG and HbA1c criteria for prediabetes at screening visit 1, 98.6% exhibited dysglycemia (defined as prediabetes or diabetes) on repeat testing (84.5% were classified as having prediabetes, 14.1% were reclassified as having diabetes). Of those with diabetes, 62.6% were identified by 2hPG alone. CONCLUSIONS: Combined measurement of FPG and HbA1c is a reliable and reproducible measure to identify presence of dysglycemia among people at high risk. A prediction model is provided to help clinicians decide whether an oral glucose tolerance test will provide value in detecting diabetes based on the 2hPG criterion.

Value of early postoperative random growth hormone levels and nadir growth hormone levels after oral glucose tolerance testing in acromegaly.

OBJECTIVE: There is no ideal marker to identify residual tumor tissue after surgery in patients with acromegaly. The purpose was to elucidate if early postoperative hormone testing gives reliable information regarding complete resection of a GH-producing pituitary adenoma. DESIGN: Fourty-eight patients undergoing surgery for acromegaly from 04/2013-05/2014 were prospectively examined for random GH, IGF1, and GH levels after oral glucose tolerance testing (OGTT) in the early postoperative phase and on follow-up. Criterion for inclusion was a minimum follow-up of one year for each patient with respect to remission. RESULTS: Thirty-three patients showed GH suppression below 1 µg/l after OGTT in the early postoperative phase. Follow-up GH, IGF1 and OGTT tests confirmed the initial findings in 30 patients. The three remaining patients showed biochemical signs of persisting acromegaly. In the remaining 15 patients early postoperative GH suppression was above 1 µg/l. Of those, six patients went into remission during follow-up, nine patients without postoperative GH suppression <1 µg/l remained acromegalic. CONCLUSIONS: GH suppression to <1 µg/l as well as random GH levels below 1 µg/l in the early postoperative phase seem to be of good positive predictive value for long-term remission. However, several patients without suppression of GH to <1 µg/l in the early postoperative OGTT went into delayed remission. These results have to be taken into account prior to initiation of further therapy.

Prediction of gestational diabetes mellitus in the Born in Guangzhou Cohort Study, China.

OBJECTIVE: To assess potential risk factors in identifying women at risk for gestational diabetes mellitus (GDM). METHODS: The present study included data collected as part of a prospective cohort study, and included women with singleton pregnancies who underwent initial prenatal examination at a tertiary women and children's hospital in Guangzhou, China between February 1, 2012, and December 31, 2015. Maternal characteristics and medical history were investigated to evaluate associations with GDM. A risk factor scoring system for the prediction of GDM was generated using logistic regression. RESULTS: Overall, 1129 (13.5%) of 8381 women were diagnosed with GDM. Women older than 35 years had a 3.95-fold increased risk of GDM (95% confidence interval 2.80-5.58) compared with women aged 16-25 years; obese women had a 6.54-fold higher risk (95% confidence interval 3.50-12.23) compared with underweight women. A risk scoring system was established based on age, body mass index, family history of diabetes, weight gain, and history of GDM. Screening for women with a score of 12 or more would have reduced the number undergoing oral glucose tolerance testing by 2131 (25.4%) patients with a sensitivity of 87% for GDM detection. CONCLUSION: The assessment of risk factors for GDM could provide a foundation for improving risk-based screening strategies in this and similar populations.

Alpha-Lipoic Acid Shows Promise to Improve Migraine in Patients with Insulin Resistance: A 6-Month Exploratory Study.

Alpha-lipoic acid (ALA) is known to lower insulin resistance (IR), which is common among migraineurs. To assess the effect of ALA on headache in migraineurs with IR, we performed an exploratory study on a cohort of patients with migraine, followed at our Headache Center. The 32 patients took ALA 400 mg b.i.d. for 6 months in addition to their on-going treatment. The percentage of patients with a reduction of at least 50% of the attacks was 0.53 (confidence interval [95% CI] 0.36-0.70) at 2 months, 0.56 (0.39-0.73) at 4 months, and 0.69 (0.53-0.85) at 6 months. The incidence rate ratio of attacks at 6 months versus baseline was 0.48 (0.43-0.53, P < .001), corresponding to a mean (95% CI) number of attacks of 5 (4-6) versus 11 (10-12). The number of days of treatment in the previous month was 7.7 (6.8-8.7) at baseline, 5.4 (4.6-6.2) at 2 months, 5.3 (4.5-6.1) at 4 months, and 4.3 (3.6-5.0) at 6 months. Baseline and 120-min glucose and insulin and quantitative insulin sensitivity check index (QUICKI) and the Stumvoll index did not change at 6 months versus baseline. This exploratory study shows that the administration of ALA may be associated with a reduction in the number of attacks and the days of treatment in migraineurs with IR. A randomized controlled trial is needed to test this possibility.

"Silent" Diabetes and Clinical Outcome After Treatment With Contemporary Drug-Eluting Stents: The BIO-RESORT Silent Diabetes Study.

OBJECTIVES: This study sought to assess the prevalence and clinical impact of silent diabetes and pre-diabetes in "nondiabetic" percutaneous coronary intervention (PCI) all-comers. BACKGROUND: Patients with undetected and thus untreated (silent) diabetes may have higher event risks after PCI with contemporary drug-eluting stents (DES). METHODS: The BIO-RESORT Silent Diabetes study, performed at Thoraxcentrum Twente, is a substudy of the randomized multicenter BIO-RESORT (BIOdegradable Polymer and DuRable Polymer Drug-eluting Stents in an All COmeRs PopulaTion) trial (NCT01674803). Patients underwent oral glucose tolerance testing (OGTT), and assessment of glycosylated hemoglobin with fasting plasma glucose. Primary endpoint was a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization at 1 year. RESULTS: Of the 988 participants, OGTT detected silent diabetes in 68 (6.9%), pre-diabetes in 133 (13.3%), and normal glucose metabolism in 788 (79.8%). Patients with silent diabetes had higher primary endpoint rates (13.2% vs. 7.6% vs. 4.8%; p < 0.001; silent diabetes vs. normal: hazard ratio: 4.2; 95% confidence interval: 1.9 to 9.2). Differences were driven by myocardial infarction (p < 0.001) which occurred mostly <48 h. Based on glycosylated hemoglobin and fasting plasma glucose, silent diabetes was found in 33 (3.3%) patients, pre-diabetes in 217 (22.0%) patients, and normal glucose metabolism in 738 (74.7%) patients; primary endpoint rates were similar to OGTT-based analyses (12.1% vs. 5.5% vs. 3.1%; p = 0.01). Multivariate analyses demonstrated that abnormal glucose metabolism by either diagnostic approach, present in 330 (33.4%) patients, independently predicted adverse event risk (hazard ratio: 2.2; 95% confidence interval: 1.2 to 4.2). CONCLUSIONS: Abnormal glucose metabolism was detected in 1 of 3 "nondiabetic" PCI patients and was independently associated with up to 4-fold higher event risks. Future intervention trials should determine whether meaningful benefits accrue from routine glycemia testing in such patients.

Serum perfluorinated chemicals, glucose homeostasis and the risk of diabetes in working-aged Taiwanese adults.

BACKGROUND: The link among perfluoroalkyl and polyfluoroalkyl substances (PFASs), abnormal glucose homeostasis and the risk of diabetes has been intensively debated with conflicting evidence. OBJECTIVES: We evaluated the associations among PFASs, oral glucose tolerance testing (OGTT) curves and diabetes prevalence in 571 working-aged Taiwanese participants. METHODS: Exposure measures included serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA). Outcomes were OGTT curves and prevalent diabetes defined by fasting blood glucose (FBG) ≥126mg/dL, 2-h glucose ≥200mg/dL, or glycated hemoglobin ≥6.5%. Analyses were performed with multiple logistic regression and functional data analysis. RESULTS: A total of 39 participants (6.8%) had diabetes in this study. After full adjustment, the increase in the geometric means of FBG, 2-h glucose concentrations, and area under the OGTT curve (AUC120) with a doubling increase in PFOS was 3% (95% CI 1-4), 8% (5-12), and 6% (4-9), respectively. Compared to the lowest-quartile of PFOS concentrations (<2.4ng/ml), the OGTT trajectories were significantly steeper in participants of the highest-quartile PFOS exposure (>4.8ng/ml) and the vertical shifting of the mean curve for each PFOS quartile showed a dose-response pattern. The adjusted odds ratio for diabetes comparing the highest to lowest quartile was 3.37 (95% CI 1.18-9.65). For PFOA, PFNA, and PFUA, the opposite pattern of OGTT trajectory and the opposite risk profile for diabetes were observed. CONCLUSIONS: Chronic PFOS exposure was associated with impaired glucose homeostasis and the increased prevalence of diabetes. However, PFOA, PFNA, and PFUA showed a potential protective effect against glucose intolerance and the risk of diabetes. Future research focusing on clarifying possible differential effects of different species of PFASs on glucose homeostasis and establishing the prospective associations between PFASs and diabetes is needed.

Measuring visfatin levels in saliva: an alternative approach to gestational diabetes screening

ABSTRACT Objective: Oral glucose tolerance testing (OGTT) is the current recommended approach for the diagnosis of gestational diabetes mellitus (GDM). Visfatin is a type of novel adipokine of interest that mostly participates in glucose metabolism and inflammatory processes. We aim to identify a screening technique for GDM using salivary visfatin levels and to establish this technique's value as a screening method compared to OGTT. Materials and methods: This is a cross-sectional case-control study. The cohort was formed from the saliva samples of pregnant patients in their 24th through 28th weeks of gestation. Patients were divided into two groups depending on their GDM status. OGTT and visfatin test results were compared and subjected to further analysis to establish a cutoff value for visfatin testing. Results: ELISA results indicated a significant difference between patients with GDM compared to patients without GDM; the values were 18.89 ± 9.59 and 12.44 ± 8.75, respectively (p: 0.007). A cutoff value of 10.5 ng/mL can be used to detect GDM with 78% sensitivity and 51% specificity. Conclusion: Salivary visfatin levels were significantly higher in patients with GDM. The existence of a differential in the concentration of visfatin in saliva can be utilized to develop a new screening method for GDM.