We present a sensing system operating at millimetre (mm) waves in transmission mode that can measure glucose level changes based on the complex permittivity changes across the signal path. The ...permittivity of a sample can change significantly as the concentration of one of its substances varies: for example, blood permittivity depends on the blood glucose levels. The proposed sensing system uses two facing microstrip patch antennas operating at 60 GHz, which are placed across interrogated samples. The measured transmission coefficient depends on the permittivity change along the signal path, which can be correlated to the change in concentration of a substance. Along with theoretical estimations, we experimentally demonstrate the sensing performance of the system using controlled laboratory samples, such as water-based glucose-loaded liquid samples. We also present results of successful glucose spike detection in humans during an in-vivo Intravenous Glucose Tolerance Test (IVGTT). The system could eventually be developed into a non-invasive glucose monitor for continuous monitoring of glucose levels for people living with diabetes, as it can detect as small as 1.33 mmol/l (0.025 wt%) glucose concentrations in the controlled water-based samples satisfactorily, which is well below the typical human glucose levels of 4 mmol/l.
Aims/hypothesis
Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis (CF) and its presence is associated with adverse effects on nutritional status and pulmonary ...function. Early diagnosis could minimise CFRD morbidity, yet current methods of an OGTT at 0 and 2 h yield unreliable results. Our aim was to determine which indices from a 2 h OGTT with sampling every 30 min might improve prediction of CFRD.
Methods
Cross-sectional analysis at baseline (
n
= 293) and observational prospective analysis (
n
= 185; mean follow-up of 7.5 ± 4.2 years) of the Montreal Cystic Fibrosis Cohort were performed. Blood glucose and insulinaemia OGTT variables were studied in relation to lung function (forced expiratory volume in 1 s FEV1), BMI and risk of developing CFRD.
Results
At baseline, maximum OGTT glucose (G
max
) was negatively associated with FEV1 (
p
= 0.003). Other OGTT values, including classical 2 h glucose, were not. A higher G
max
was associated with lower insulin secretory capacity, delayed insulin peak timing and greater pancreatic insufficiency (
p
< 0.01). G
max
was positively associated with the risk of developing CFRD (
p
= 0.0029); no individual with a G
max
< 8 mmol/l developed CFRD over the following decade. No OGTT variable correlated to the rate of change in BMI or FEV1.
Conclusions/interpretation
In adults with CF, G
max
is strongly associated with the risk of developing CFRD; G
max
< 8 mmol/l could identify those at very low risk of future CFRD. G
max
is higher in individuals with pancreatic insufficiency and is associated with poorer insulin secretory capacity and pulmonary function.
Graphical abstract
1 Department of Information Engineering, University of Padua, Padua, Italy; 2 San Raffaele Scientific Institute, Milan, Italy; 3 Larry Hillblom Islet Research Center, David Geffen School of Medicine, ...University of California, Los Angeles, California; and 4 Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota
Submitted 16 August 2006
; accepted in final form 27 February 2007
Assessment of insulin secretion in humans under physiological conditions has been a challenge because of its complex interplay with insulin action and hepatic insulin extraction. The possibility of simultaneously assessing -cell function, insulin sensitivity, and hepatic insulin extraction under physiological conditions using a simple protocol is appealing, since it has the potential to provide novel insights regarding the regulation of fasting and postprandial glucose metabolism in diabetic and nondiabetic humans. In this Perspective, we review data indicating that an oral glucose tolerance test (OGTT) or a meal test is able to accomplish this goal when interpreted with the oral -cell minimal model. We begin by using the well-established intravenous minimal model to highlight how the oral minimal model was developed and how the oral assessment parallels that of an intravenous glucose tolerance test (IVGTT). We also point out the unique aspects of both approaches in relation to their ability to assess different aspects of the -cell secretory cascade. We review the ability of the oral model to concurrently measure insulin sensitivity and hepatic insulin extraction, thereby enabling it to quantitatively portray the complex relationship among -cell function, hepatic insulin extraction, and insulin action. In addition, data from 204 individuals (54 young and 159 elderly) who underwent both IVGTT and meal tolerance tests are used to illustrate how these different approaches provide complementary but differing insights regarding the regulation of -cell function in humans.
glucose tolerance; disposition index; oral glucose tolerance test; meal; intravenous glucose tolerance test
Address for reprint requests and other correspondence: C. Cobelli, Dept. of Information Engineering, Univ. of Padua, Via Gradenigo 6/B, 35131 Padua, Italy (e-mail: cobelli{at}dei.unipd.it )
The aim of the study was to evaluate glucose and insulin metabolism of cows receiving a supplementation of biotin (B8), folic acid (B9), and vitamin B12 (B12) during the transition period. According ...to a 2 × 2 factorial arrangement, 32 cows were randomly assigned to 9 incomplete blocks according to their previous 305-d milk yield. Within each block, cows were randomly assigned to 1 of the following levels of biotin from −27 to 28 d relative to the parturition: (1) no biotin supplement (B8−) or (2) 20 mg/d of dietary biotin (B8+). Within each level of biotin, the cows received either (1) 2-mL weekly intramuscular injections of saline 0.9% NaCl (B9B12−) or (2) 2.6 g/d of dietary folic acid and 2-mL weekly intramuscular injections of 10 mg of vitamin B12 (B9B12+). An intravenous glucose tolerance test was performed at 25 d in milk. Baseline plasma glucagon, glucose, and nonesterified fatty acid concentrations did not differ among treatments. For B9B12+ cows, baseline plasma insulin concentration and maximal glucose concentration after glucose administration were greater when also combined with biotin compared with no biotin combination, whereas there was no effect in B9B12− cows. There was no treatment effect on time to reach half-maximal glucose and insulin concentrations, glucose positive incremental area under the curve, and glucose and insulin clearance rates. Regarding insulin results, maximal plasma concentration and positive incremental area under the curve were respectively 51 and 74% greater for cows receiving the B8 supplement than for cows who did not. Moreover, plasma nonesterified fatty acid concentration nadir tended to be reached later for B8 cows. Insulin peak was reached earlier for cows in the group B9B12+ than cows in B9B12−, regardless of B8 supplementation. Under the current conditions, our results suggested that cows receiving a B8 supplement had a reduced insulin sensitivity in early lactation. Insulin response was faster for B9B12+ cows, but this was not translated into further improvements following the glucose administration challenge.
Impaired insulin sensitivity is a key abnormality underlying the development of type 2 diabetes. Measuring insulin sensitivity is therefore of importance in identifying individuals at risk of ...developing diabetes and for the evaluation of diabetes-focused interventions. A number of measures have been proposed for this purpose. Among these the hyperinsulinemic euglycemic clamp (HEC) is considered the gold standard. However, as the HEC is a costly, time consuming and invasive method requiring trained staff, there is a need for simpler so called surrogate measures.
A frequently used approach to evaluate surrogate measures is through correlation with the HEC. We discuss limitations with this method. We suggest other aspects to take into consideration, such as repeatability, reproducibility, systematic biases and discrimination ability. In addition, we focus on three frequently used surrogate measures. We argue that they are one-to-one transformations of each other, and therefore question the benefits of further comparison between them. They give the same results in all rank-based methods, for instance Spearman correlations, Mann-Whitney tests and receiver operating characteristic (ROC) analysis.
We suggest investigating further aspects than correlation alone when evaluating a surrogate measure of insulin sensitivity. We recommend choosing one of the three surrogate measures HOMA-IR, QUICKI and FIRI for analysis of a clinical study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy.
In a secondary analysis of a longitudinal study, participants were studied ...prepregnancy (n = 40), in early pregnancy (n = 36; 12-14 weeks' gestation), and in late pregnancy (n = 36; 34-36 weeks' gestation). Participants underwent an OGTT, an intravenous glucose tolerance test (IVGTT), and a hyperinsulinemic-euglycemic clamp at each timepoint. We calculated homeostatic model assessment of beta-cell function (HOMA-2B), insulinogenic index (IGI), corrected insulin response (CIR), ratio of the area under the insulin curve and the area under the glucose curve (AUCins/AUCglu), and Stumvoll first-phase estimate (Stumvoll) from OGTT insulin and glucose levels. We used Pearson correlation to compare measures from OGTT and IVGTT. We used mixed effects models to examine longitudinal changes in insulin secretory response.
Stumvoll was the only OGTT-based measure that was significantly correlated with first-phase insulin response prior to and across gestation (prepregnancy: r = 0.44, P = 0.01; early pregnancy: r = 0.67, P = 0.0001; late pregnancy: r = 0.67, P = 0.0001). In early and late pregnancy, AUCins/AUCglu had the strongest correlation with first-phase insulin response (early pregnancy: r = 0.79, P < 0.0001; late pregnancy: r = 0.69, P < 0.0001) but was not significantly correlated prepregnancy. IGI and CIR were significantly correlated with first-phase insulin response prepregnancy (IGI: r = 0.50, P = 0.005; CIR r = 0.47, P = 0.008) and in late pregnancy (IGI: r = 0.68, P = 0.0001; CIR r = 0.57, P = 0.002) but not in early pregnancy. HOMA-2B was the weakest correlate of first-phase insulin response. Stumvoll and AUCins/AUCglu recapitulated the longitudinal changes in insulin secretory response observed by IVGTT.
Stumvoll and AUCins/AUCglu are valid OGTT-based insulin secretory response measures for pregnancy studies.
Introduction: Surgical remission for acromegaly is dependent on a number of factors including tumour size, invasiveness, and surgical expertise. We studied the value of early post-operative growth ...hormone (GH) level as a predictor of outcome and to guide early surgical re-exploration for residual disease in patients with acromegaly. Methods: Patients with acromegaly undergoing first-time endoscopic transsphenoidal surgery between 2005 and 2015, in 2 regional neurosurgical centres, were studied. Insulin-like growth factor-1 (IGF-1), basal GH (i.e., sample before oral glucose), and GH nadir on oral glucose tolerance test (OGTT) were tested at various time points, including 2–5 days post-operatively. Definition of disease remission was according to the 2010 consensus statement (i.e., GH nadir <0.4 μg/L during an OGTT and normalized population-matched IGF-1). Forward stepwise logistic regression was used to determine factors associated with remission. Results: We investigated 81 consecutive patients with acromegaly, 67 (83%) of which had macroadenomas and 22 (27%) were noted to be invasive at surgery. Mean follow-up was 44 ± 25 months. Overall, surgical remission was achieved in 55 (68%) patients at final follow-up. On univariate analysis, the remission rates at the end of the study period for patients with early post-operative GH nadir on OGTT of <0.4 (N = 43), between 0.4 and 1 (N = 28), and >1 μg/L (N = 8) were 88, 54, and 20%, respectively. Similar results were seen with basal GH on early post-operative OGTT. On multivariate regression analysis, pre-operative IGF-1 (odds ratio of 13.1) and early post-operative basal GH (odds ratio of 5.0) and GH nadir on OGTT (odds ratio of 6.8) were significant predictors of residual disease. Based on a raised early GH nadir and post-operative MR findings, 10 patients underwent early surgical re-exploration. There was reduction in post-operative GH levels in 9 cases, of which 5 (50%) achieved long-term remission. There was an increased risk of new pituitary hormone deficiencies in patients having surgical re-exploration compared to those having a single operation (60 vs. 14%). Conclusions: An early post-operative basal GH and GH nadir on OGTT are reliable predictors of long-term disease remission. It can be used to guide patients for early surgical re-exploration for residual disease, although there is increased risk of hypopituitarism.
To understand the effect of 50-g oral glucose tolerance test (OGTT) on fetal celiac artery and superior mesenteric artery (SMA) Doppler parameters.
A total of 43 healthy pregnant women followed ...in our hospital were included in the study. All Doppler parameters of the celiac artery and SMA (peak systolic velocity (PSV); pulsatility index (PI); resistance index (RI); systolic/diastolic ratio (SD); time average maximum velocity (TAMAX)) were obtained by ultrasonography before and 1 h after OGTT.
The mean PSV value of the celiac artery decreased statistically significantly after OGTT (37.29 ± 11.96 cm/s; 29.51 ± 10.07 cm/s; p=0.002). While the mean of the PI was 2.09 ± 0.57 before the test, it was found to be 1.84 ± 0.64 after the test (p=0.027). Mean PSV (39.82 ± 13.07 cm/s; 35.19 ± 15.27 cm/s; p=0.104) and PI (2.21 ± 0.65; 2.11 ± 0.80; p=0.375) values of SMA were also found to be decreased without statistically significancy.
The data obtained from our study reveals that the PSV and PI values of celiac artery and SMA slightly decrease after OGTT.
The diagnosis of hyperglycaemia in sub-Saharan Africa (SSA) is challenging. Blood glucose levels obtained during oral glucose tolerance test (OGTT) may not reflect home glycaemic profiles. We compare ...OGTT results with home glycaemic profiles obtained using the FreeStyle Libre continuous glucose monitoring device (FSL-CGM).
Twenty-eight women (20 with gestational diabetes GDM, 8 controls) were recruited following OGTT between 24 and 28 weeks of gestation. All women wore the FSL-CGM device for 48-96 h at home in early third trimester, and recorded a meal diary. OGTT was repeated on the final day of FSL-CGM recording. OGTT results were compared with ambulatory glycaemic variables, and repeat OGTT was undertaken whilst wearing FSL-CGM to determine accuracy of the device.
FSL-CGM results were available for 27/28 women with mean data capture 92.8%. There were significant differences in the ambulatory fasting, post-prandial peaks, and mean glucose between controls in whom both primary and secondary OGTT was normal (n = 6) and those with two abnormal OGTTs or "true" GDM (n = 7). There was no difference in ambulatory mean glucose between these controls and the 13 women who had an abnormal primary OGTT and normal repeat OGTT. These participants had significantly lower body mass index (BMI) than the true GDM group (29.0 Vs 36.3 kg/m
, p-value 0.014). Paired OGTT/FSL-CGM readings revealed a Mean Absolute difference (MAD) -0.58 mmol/L and Mean Absolute Relative Difference (MARD) -11.9%. Bland-Altman plot suggests FSL-CGM underestimated blood glucose by approximately 0.78 mmol/L.
Diagnosis of GDM on a single OGTT identifies a proportion of women who do not have a significantly higher home glucose levels than controls. This raises questions about factors which may affect the reproducibility of OGTT in this population, including food insecurity and atypical phenotypes of diabetes. More investigation is needed to understand the suitability of the OGTT as a diagnostic test in sub-Saharan Africa.
Background
Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. Although GDM usually resolves following birth, it is associated with significant morbidities for mothers ...and their infants in the short and long term. There is strong evidence to support treatment for GDM. However, there is uncertainty as to whether or not screening all pregnant women for GDM will improve maternal and infant health and if so, the most appropriate setting for screening. This review updates a Cochrane Review, first published in 2010, and subsequently updated in 2014.
Objectives
To assess the effects of screening for gestational diabetes mellitus based on different risk profiles and settings on maternal and infant outcomes.
Search methods
We searched Cochrane Pregnancy and Childbirth's Trials Register (31 January 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (14 June 2017), and reference lists of retrieved studies.
Selection criteria
We included randomised and quasi‐randomised trials evaluating the effects of different protocols, guidelines or programmes for screening for GDM based on different risk profiles and settings, compared with the absence of screening, or compared with other protocols, guidelines or programmes for screening. We planned to include trials published as s only and cluster‐randomised trials, but we did not identify any. Cross‐over trials are not eligible for inclusion in this review.
Data collection and analysis
Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included trials. We resolved disagreements through discussion or through consulting a third reviewer.
Main results
We included two trials that randomised 4523 women and their infants. Both trials were conducted in Ireland. One trial (which quasi‐randomised 3742 women, and analysed 3152 women) compared universal screening versus risk factor‐based screening, and one trial (which randomised 781 women, and analysed 690 women) compared primary care screening versus secondary care screening. We were not able to perform meta‐analyses due to the different interventions and comparisons assessed.
Overall, there was moderate to high risk of bias due to one trial being quasi‐randomised, inadequate blinding, and incomplete outcome data in both trials. We used GRADEpro GDT software to assess the quality of the evidence for selected outcomes for the mother and her child. Evidence was downgraded for study design limitations and imprecision of effect estimates.
Universal screening versus risk‐factor screening (one trial)
Mother
More women were diagnosed with GDM in the universal screening group than in the risk‐factor screening group (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.12 to 3.04; participants = 3152; low‐quality evidence). There were no data reported under this comparison for other maternal outcomes including hypertensive disorders of pregnancy, caesarean birth, perineal trauma, gestational weight gain, postnatal depression, and type 2 diabetes.
Child
Neonatal outcomes: large‐for‐gestational age, perinatal mortality, mortality or morbidity composite, hypoglycaemia; and childhood/adulthood outcomes: adiposity, type 2 diabetes, and neurosensory disability, were not reported under this comparison.
Primary care screening versus secondary care screening (one trial)
Mother
There was no clear difference between the primary care and secondary care screening groups for GDM (RR 0.91, 95% CI 0.50 to 1.66; participants = 690; low‐quality evidence), hypertension (RR 1.41, 95% CI 0.77 to 2.59; participants = 690; low‐quality evidence), pre‐eclampsia (RR 0.80, 95% CI 0.36 to 1.78; participants = 690;low‐quality evidence), or caesarean section birth (RR 1.00, 95% CI 0.80 to 1.27; participants = 690; low‐quality evidence). There were no data reported for perineal trauma, gestational weight gain, postnatal depression, or type 2 diabetes.
Child
There was no clear difference between the primary care and secondary care screening groups for large‐for‐gestational age (RR 1.37, 95% CI 0.96 to 1.96; participants = 690; low‐quality evidence), neonatal complications: composite outcome, including: hypoglycaemia, respiratory distress, need for phototherapy, birth trauma, shoulder dystocia, five minute Apgar less than seven at one or five minutes, prematurity (RR 0.99, 95% CI 0.57 to 1.71; participants = 690; low‐quality evidence), or neonatal hypoglycaemia (RR 1.10, 95% CI 0.28 to 4.38; participants = 690; very low‐quality evidence). There was one perinatal death in the primary care screening group and two in the secondary care screening group (RR 1.10, 95% CI 0.10 to 12.12; participants = 690; very low‐quality evidence). There were no data for neurosensory disability, or childhood/adulthood adiposity or type 2 diabetes.
Authors' conclusions
There are insufficient randomised controlled trial data evaluating the effects of screening for GDM based on different risk profiles and settings on maternal and infant outcomes. Low‐quality evidence suggests universal screening compared with risk factor‐based screening leads to more women being diagnosed with GDM. Low to very low‐quality evidence suggests no clear differences between primary care and secondary care screening, for outcomes: GDM, hypertension, pre‐eclampsia, caesarean birth, large‐for‐gestational age, neonatal complications composite, and hypoglycaemia.
Further, high‐quality randomised controlled trials are needed to assess the value of screening for GDM, which may compare different protocols, guidelines or programmes for screening (based on different risk profiles and settings), with the absence of screening, or with other protocols, guidelines or programmes. There is a need for future trials to be sufficiently powered to detect important differences in short‐ and long‐term maternal and infant outcomes, such as those important outcomes pre‐specified in this review. As only a proportion of women will be diagnosed with GDM in these trials, large sample sizes may be required.
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