The WHO 2013 oral glucose tolerance test: The utility of isolated glucose measurements - A retrospective cohort study.

OBJECTIVE: The WHO 2013 guidelines recommend screening for gestational diabetes mellitus (GDM) by 3-point oral glucose tolerance test (OGTT). The objective of this retrospective cohort study was to evaluate GDM diagnosed by an isolated high glucose. STUDY DESIGN: We included pregnant women deemed at risk for GDM were offered GDM screening. We examined the records of 1939 consecutively screened pregnancies at two teaching hospitals in Amsterdam during 2016-2020. Using the WHO 2013 diagnostic criteria, we calculated the proportion of GDM cases diagnosed by isolated abnormal glucose values. RESULTS: Among those screened in our high risk cohort, GDM incidence was 31.5%. Of the GDM diagnoses, 57.0% were based on an isolated fasting glucose value, 30.9% based on multiple raised glucose measurements, 7.4% on an isolated raised 2-hour glucose and 4.7% on an isolated raised 1-hour glucose. For 1-hour glucose, the number needed to screen was 67 persons for one additional GDM case. CONCLUSION: The 1-hour glucose in the 3 point OGTT, as suggested by the WHO 2013 guidelines for GDM, contributes only small numbers of GDM cases and a high number needed to screen (67 for 1 additional case in a selective high risk GDM screening strategy), and is likely even less effective in universally screened populations.

Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.

AIMS: The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes. METHODS: A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup. RESULTS: We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow-up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between-studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details. CONCLUSION: This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high-quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.

Explaining unexplained hypoglycemia: How LC-MS/MS can help.

Explaining hypoglycaemia, especially in patients without diabetes mellitus, is challenging. Here we present a case, where the added value for clinical diagnosis of insulin determination with liquid chromatography-mass spectrometry (LC-MS/MS) is shown. By the use of LC-MS/MS the different insulin analogues can be identified. The confirmation of an insulin analogue present during hypoglycaemia facilitated in our case the discussion with the patient and his family about what happened.

Effects of surgery and general anaesthesia on sleep-wake timing: CLOCKS observational study.

Surgery and general anaesthesia have the potential to disturb the body's circadian timing system, which may affect postoperative outcomes. Animal studies suggest that anaesthesia could induce diurnal phase shifts, but clinical research is scarce. We hypothesised that surgery and general anaesthesia would result in peri-operative changes in diurnal sleep-wake patterns in patients. In this single-centre prospective cohort study, we recruited patients aged ≥18 years scheduled for elective surgery receiving ≥30 min of general anaesthesia. The Munich Chronotype Questionnaire and Pittsburgh Sleep Quality Index were used to determine baseline chronotype, sleep characteristics and sleep quality. Peri-operative sleeping patterns were logged. Ninety-four patients with a mean (SD) age of 52 (17) years were included; 56 (60%) were female. The midpoint of sleep (SD) three nights before surgery was 03.33 (55 min) and showed a phase advance of 40 minutes to 02.53 (67 min) the night after surgery (p < 0.001). This correlated with the midpoint of sleep three nights before surgery and was not associated with age, sex, duration of general anaesthesia or intra-operative dexamethasone use. Peri-operatively, patients had lower subjective sleep quality and worse sleep efficiency. Disruption started from one night before surgery and did not normalise until 6 days after surgery. We conclude that there is a peri-operative phase advance in midpoint of sleep, confirming our hypothesis that surgery and general anaesthesia disturb the circadian timing system. Patients had decreased subjective sleep quality, worse sleep efficiency and increased daytime fatigue.

Characteristics associated with polypharmacy in people with type 2 diabetes: the Dutch Diabetes Pearl cohort.

AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.

Falsely decreased thyroglobulin levels in a patient with differentiated thyroid carcinoma.

We describe a case of a patient with metastasized differentiated thyroid carcinoma who was treated with total thyroidectomy followed-up by radioactive iodine treatment. During treatment and follow-up the thyroglobulin levels were assayed which surprisingly did not match the clinical condition. An analytical flaw was suspected. Re-analysis in the laboratory showed the presence of a high dose hook effect (HDH), resulting in falsely low Tg levels. This case shows that HDH effects in immunoassays, like the thyroglobulin assay, still exist in daily practice. Discordance between laboratory results and clinical condition underlines the importance of short lines of communication between clinical chemists and medical doctors.

A randomized clinical trial comparing the effect of basal insulin and inhaled mealtime insulin on glucose variability and oxidative stress.

AIM: To assess the effect of three times daily mealtime inhaled insulin therapy compared with once daily basal insulin glargine therapy on 72-h glucose profiles, glucose variability and oxidative stress in type 2 diabetes patients. METHODS: In an inpatient crossover study, 40 subjects with type 2 diabetes were randomized to receive 9 days of inhaled insulin three times daily before meals or 9 days of glargine administered in the morning before breakfast in a randomized order. During the last 72 h in each phase, glucose was measured with continuous glucose monitoring. Activation of oxidative stress was measured by determining the 15(S)-8-iso-PGF(2alpha)-secretion in 24-h urine samples. RESULTS: Inhaled insulin improved overall and postprandial glucose control significantly better than insulin glargine (p < 0.0001). There was a trend towards a greater reduction in glucose variability (8-9%) in the inhaled group [p = 0.1430 and p = 0.3298 for mean amplitude of glycaemic excursions (MAGEs) and mean of daily differences respectively]. Oxidative stress, estimated by determining the urinary isoprostane excretion (15(S)-8-iso-PGF(2alpha)), was equally reduced from baseline by both treatments. No correlation was found between glucose variability and oxidative stress in both groups. CONCLUSIONS: This study showed a mealtime insulin approach to improve glycaemic control more than a basal insulin approach. These findings indicate also that lowering glucose using insulin treatment lowers oxidative stress over time, at least for the study period of 9 days, in type 2 diabetes patients. Contrary to earlier data, we found no correlation between glucose variability (MAGE) and oxidative stress (15(S)-8-iso-PGF(2alpha)) in this study.

The auditory startle response in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) patients are considered to have excessive EMG responses in the orbicularis oculi (OO) muscle and excessive autonomic responses to startling stimuli. The aim of the present study was to gain more insight into the pattern of the generalized auditory startle reflex (ASR). Reflex EMG responses to auditory startling stimuli in seven muscles rather than the EMG response of the OO alone as well as the psychogalvanic reflex (PGR) were studied in PTSD patients and healthy controls. Ten subjects with chronic PTSD (>3 months) and a history of excessive startling and 11 healthy controls were included. Latency, amplitude and duration of the EMG responses and the amplitude of the PGR to 10 auditory stimuli of 110 dB SPL were investigated in seven left-sided muscles. The size of the startle reflex, defined by the number of muscles activated by the acoustic stimulus and by the amplitude of the EMG response of the OO muscle as well, did not differ significantly between patients and controls. Median latencies of activity in the sternocleidomastoid (SC) (patients 80 ms; controls 54 ms) and the deltoid (DE) muscles (patients 113 ms; controls 69 ms) were prolonged significantly in PTSD compared to controls (P < 0.05). In the OO muscle, a late response (median latency in patients 308 ms; in controls 522 ms), probably the orienting reflex, was more frequently present in patients (56%) than in controls (12%). In patients, the mean PGR was enlarged compared to controls (P < 0.05). The size of the ASR response is not enlarged in PTSD patients. EMG latencies in the PTSD patients are prolonged in SC and DE muscles. The presence of a late response in the OO muscle discriminates between groups of PTSD patients with a history of startling and healthy controls. In addition, the autonomic response, i.e. the enlarged amplitude of the PGR can discriminate between these groups.