- Ann Robinson, NHS GP and health writer and broadcaster
Covid, babies, and type 1 diabetes
There’s been a reported rise in diabetes in children since the covid pandemic, and, although some of that rise might be a backlog in accessing care, it is unclear whether covid itself has triggered diabetes, especially in those who are genetically susceptible.
In this European longitudinal cohort study of 885 infants with a high (>10%) genetic risk of type 1 diabetes, islet autoantibodies (IAbs)—a harbinger of diabetes development within 10 years—were substantially more likely to develop in those who had had covid (demonstrated by covid antibodies) than in those who hadn’t (7.8 v 3.5 per 100 person-years). Peak vulnerability for developing IAbs in response to viral infection is thought to be around 12 months, which was borne out in this study. Although there was a spike in IAbs associated with covid infection, overall there was no rise in IAbs during the pandemic period, probably because there was a fall in other respiratory infections during successive lockdowns and social distancing measures. However, whether the rise in IAbs specifically associated with covid infection results in more diabetes cases down the line, still remains to be seen.
JAMA doi:10.1001/jama.2023.16348
New normals
In a world of uncertainties, one metric that I thought was set in stone is that normal body temperature is 37°C. In fact, human body temperature has been falling by 0.03°C per decade for at least the past 200 years, probably because our metabolic rate has fallen as we are exposed to less chronic inflammation from infections and bad teeth.
In this cross-sectional study using machine learning in 618 306 adult outpatient encounters, the mean “normal” temperature was 36.64°C (range 36.24-36.89°C). Age, sex, height, weight, and time of day were all important variables. Oral temperature rises through the day and peaks in the afternoon, is higher in women, and declines with age. In men, greater weight is associated with higher mean temperatures.
The practical significance is that in a skinny, older man who would be expected to run a temperature of 36.2-36.4°C, a reading of 37°C might represent underlying disease. Setting reliable “normals” is yet another way in which machine learning tools can help us to refine what we do. Getting a reliable thermometer is another.
JAMA Intern Med doi:10.1001/jamainternmed.2023.4291
Belt and braces
Emergency contraception in the form of levonorgestrel 1.5 mg is effective at preventing pregnancy if taken within 72 hours of unprotected sex. According to a new study, adding the non-steroidal anti-inflammatory piroxicam (40 mg) makes it even more effective, probably because NSAIDs reduce prostaglandins, which are involved in many aspects of conception.
Of 860 women presenting for emergency contraception at a Hong Kong clinic, there was one pregnancy in the levonorgestrel and piroxicam group compared with seven pregnancies in the levonorgestrel and placebo group, out of a potential 17 pregnancies without emergency contraception. There was no difference in side effects; most women didn’t miss a period, and 40% had some vaginal spotting in the week after emergency contraception.
The results might not apply globally as the women were mostly of Asian ethnicity with low rates of obesity (which can make emergency contraception less effective).
Lancet doi:10.1016/S0140-6736(23)01240-0
Weighty matters
Glucagon-like peptide-1 (GLP-1) analogues such as semaglutide and liraglutide help people to lose excess weight by decreasing appetite and delaying gastric emptying. Both are available as subcutaneous injections, but the race is on to develop an oral formulation that can be absorbed from the stomach and is effective in treating both type 2 diabetes and obesity.
This phase 2 trial of 272 overweight but non-diabetic people with mean body mass index of 37.9 found that orforglipron, a once-daily formulation that combines oral semaglutide (14 mg) with an absorption enhancer was effective (mean change from baseline in body weight at 26 weeks −8.6% to −12.6% versus −2% with placebo, maintained at 36 weeks) and safe (similar side effects to injectable GLP-1 analogues).
This pharma-sponsored trial is positive, but questions remain about long term results and safety. Are we entering an era where most of the population will take a daily pill forever to remain a healthy weight? It doesn’t feel like a sustainable response to such a widespread societal problem.
N Engl J Med doi:10.1056/NEJMoa2302392
Base editing offers hope in leukaemia
Most children with T cell acute lymphoblastic leukaemia can be treated with chemotherapy, but some will not respond and need brutal stem cell transplantation. Those who relapse after transplant have a poor prognosis with less than 15% survival.
The advent of chimeric antigen receptor (CAR) T cells for the treatment of B cell cancers is a potential life saver. But T cell cancers are more tricky because CAR T cells can turn on one another because they express the same protein that they’re designed to target. One solution is genome editing to disrupt T cell antigens such as CD7 and endogenous T cell receptors, but that process can itself cause harmful DNA damage. An alternative is base editing of T cells, which avoids the risk of DNA breaks. Interim results of this phase 1 feasibility and safety study in three children with relapsed acute lymphoblastic leukaemia shows that there’s scope for more study of this technique.
N Engl J Med doi:10.1056/NEJMoa2300709