Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

The clinical dilemma of the persistent idiopathic pneumoperitoneum: A case report.

INTRODUCTION: Idiopathic pneumoperitoneum (IP) is a rare phenomenon which merits special attention. It is defined as free intraperitoneal air which is not caused by viscus perforation and does not require surgical intervention. It is generally considered a diagnosis of exclusion and often poses a genuine diagnostic dilemma. PRESENTATION OF CASE: We present an unusual case of persistent pneumoperitoneum with no identifiable cause which was found incidentally on a computed tomography (CT) scan in a patient with chronic cough and no prior surgical history. Serial consults revealed no abdominal symptoms or signs. He was managed conservatively and remains asymptomatic despite having a persistent IP on serial radiology. DISCUSSION: To our knowledge, our case is the first in the literature of an idiopathic pneumoperitoneum that persisted on subsequent radiology and was managed successfully without surgical intervention. This is a highly important case for all practicing general surgeons to learn from as knowledge of this phenomenom may help avoid unnecessary surgical intervention and potential morbidities associated with this. CONCLUSION: IP is a diagnosis of exclusion which should only be made after surgical and non-surgical causes have been outruled. In the absence of signs of peritonitis and evidence of gastrointestinal perforation on CT, a conservative approach is warranted, allowing patients to avoid unnecessary surgical intervention.

Author Correction: Analysis of inflammatory cytokine and TLR expression levels in Type 2 Diabetes with complications.

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Analysis of inflammatory cytokine and TLR expression levels in Type 2 Diabetes with complications.

The pathogenesis and complications of type 2 diabetes (T2DM) are closely linked with defective glucose metabolism, obesity, cardiovascular disease and an inability to mount an effective immune response to certain pathogenic organisms. Perturbations in key innate immune receptors known as Toll-like receptors (TLRs) and inflammatory mediators such as IL-6, TNFα and IL-1ß have been linked with T2DM. Herein, we sought to establish whether patients with T2DM and underlying complications exhibit perturbations in cytokine and TLR expression. Serum cytokine and mRNA levels of cytokines/TLRs in monocytes (M) and neutrophils (N) were measured in a cohort of 112 diabetic patients: good glycaemic control without complications (GC), good glycaemic control with complications (GCC), poor glycaemic control without complications (PC) and poor glycaemic control with complications (PCC) and compared them with 34 non-diabetic volunteers (NGT). Serum cytokine levels were normal in all study participants. In the GC group, cytokine and TLR gene expression were enhanced compared to NGT. In contrast, suppressed cytokine and TLR gene expression were evident in PC, GCC & PCC groups when compared to the GC. In conclusion, whereas serum pro-inflammatory cytokine levels are unaltered in T2DM patients, differences in inflammatory gene profiles exist among the T2DM patient groups.

Recurrent hypoglycemia increases hypothalamic glucose phosphorylation activity in rats.

The mechanisms underpinning impaired defensive counterregulatory responses to hypoglycemia that develop in some people with diabetes who suffer recurrent episodes of hypoglycemia are unknown. Previous work examining whether this is a consequence of increased glucose delivery to the hypothalamus, postulated to be the major hypoglycemia-sensing region, has been inconclusive. Here, we hypothesized instead that increased hypothalamic glucose phosphorylation, the first committed intracellular step in glucose metabolism, might develop following exposure to hypoglycemia. We anticipated that this adaptation might tend to preserve glucose flux during hypoglycemia, thus reducing detection of a falling glucose. We first validated a model of recurrent hypoglycemia in chronically catheterized (right jugular vein) rats receiving daily injections of insulin. We confirmed that this model of recurrent insulin-induced hypoglycemia results in impaired counterregulation, with responses of the key counterregulatory hormone, epinephrine, being suppressed significantly and progressively from the first day to the fourth day of insulin-induced hypoglycemia. In another cohort, we investigated the changes in brain glucose phosphorylation activity over 4 days of recurrent insulin-induced hypoglycemia. In keeping with our hypothesis, we found that recurrent hypoglycemia markedly and significantly increased hypothalamic glucose phosphorylation activity in a day-dependent fashion, with day 4 values 2.8 ± 0.6-fold higher than day 1 (P < .05), whereas there was no change in glucose phosphorylation activity in brain stem and frontal cortex. These findings suggest that the hypothalamus may adapt to recurrent hypoglycemia by increasing glucose phosphorylation; and we speculate that this metabolic adaptation may contribute, at least partly, to hypoglycemia-induced counterregulatory failure.

Breath acetone concentration decreases with blood glucose concentration in type I diabetes mellitus patients during hypoglycaemic clamps.

Conventional wisdom is that breath acetone may be markedly elevated in type 1 diabetes, but that this only occurs during poor blood glucose control and/or intercurrent illness. In contrast, little is known about breath acetone at more representative everyday blood glucose levels in diabetes. We used selected ion flow tube mass spectrometry to monitor the breath of eight patients with type 1 diabetes mellitus during 'insulin clamp' studies in which insulin and glucose were infused into patients to lower blood glucose levels in steps from normal values into the low glucose (hypoglycaemic) range. The concentration of acetone in breath and the blood sugar concentration of the patients were monitored at each blood glucose concentration. The blood glucose level at the start of the study was typically about 6 mM L(-1), whereas the breath acetone concentration at this blood glucose level was unexpectedly variable, ranging from 1 part-per-million to 21 ppm, in contrast to what was previously believed, i.e. that type 1 diabetes mellitus is characterized by high acetone levels. In all eight patients, the breath acetone declined linearly with blood glucose concentration.