Assessment of the effect of the COVID-19 lockdown on glycaemic control in people with type 1 diabetes using flash glucose monitoring.

AIM: To describe the effect of the stringent lockdown measures, introduced in the UK on 23 March 2020 to curtail the transmission of COVID-19, on glycaemic control in people with type 1 diabetes using flash glucose monitoring. METHODS: We undertook an observational study of 572 individuals with type 1 diabetes for whom paired flash glucose monitoring data were available between early March and May 2020. The primary outcome was change in flash glucose monitoring variables. We also assessed clinical variables associated with change in glycaemic control. RESULTS: Percentage of time in range increased between March and May 2020 [median (interquartile range) 53 (41-64)% vs 56 (45-68)%; P < 0.001], with associated improvements in standard deviation of glucose (P <0.001) and estimated HbA1c (P <0.001). There was a small reduction in the number of individuals meeting the hypoglycaemia target of <5% per day (64% vs 58%; P = 0.004). Comparing changes in flash glucose monitoring data from March to May in 2019 with the same period in 2020 confirmed that these differences were confined to 2020. Socio-economic deprivation was an independent predictor of a ≥5% reduction in time in range during lockdown (odds ratio 0.45 for people in the two most affluent Scottish Index of Multiple Deprivation quintiles; P <0.001). CONCLUSIONS: Lockdown was not associated with a significant deterioration in glycaemic control in people with type 1 diabetes using flash glucose monitoring. However, socio-economic deprivation appeared to increase the risk of decline in glycaemic control, which has implications for how support is focused in challenging times.

Predictors of treatment failure, incipient hypothyroidism, and weight gain following radioiodine therapy for Graves' thyrotoxicosis.

BACKGROUND: Following radioiodine ((131)I) therapy, both late recognition of hypothyroidism and treatment failure may result in adverse outcomes. AIM: We sought to assess indicators of both incipient hypothyroidism and treatment failure following (131)I and determine factors predictive of weight gain. SUBJECTS AND METHODS: Retrospective study of 288 patients receiving (131)I for treatment of Graves' thyrotoxicosis. Primary outcome measures were thyroid status and weight change at 1 yr following (131)I. RESULTS: The treatment failure rate at 1 yr was 13.5%. Hypothyroidism developed in 80.9%, with 58.5% of patients having levels of free T4 (fT4) <6 pmol/l at diagnosis. Patients receiving thionamides before and after (131)I had significantly higher levels of treatment failure (23.3%) than those with no thionamide exposure (6.3%, p=0.003), but also had more active Graves' disease. Following (131)I, development of a detectable TSH or low-normal fT4 levels was not associated with recurrent thyrotoxicosis. Median weight gain was 5.3 kg, although patients with nadir fT4 levels <6 pmol/l gained an average 2 kg more than those with levels >6 pmol/l (p=0.05). The main predictor of weight gain was fT4 level immediately prior to treatment; those in the lowest tertile gained a median 3.1 kg whilst those in the highest tertile gained 7.4 kg (median difference 4.3 kg; 95% confidence interval: 2.5-6.2). CONCLUSIONS: Marked hypothyroidism following (131)I is common and often occurs early. Simple biochemical parameters may help identify incipient hypothyroidism and potentially limit excess weight gain. Treatment failure is common in patients with severe thyrotoxicosis and in such cases larger doses of (131)I may be warranted.

A complicated pregnancy in a patient with lipodystrophic diabetes attributable to a peroxisome proliferator-activated receptor gamma (PPARG) mutation.

BACKGROUND: We describe an unplanned pregnancy in a 19-year-old with lipodystrophic diabetes caused by a mutation in the peroxisome proliferator-activated receptor gamma (PPARG) gene. The pregnancy was complicated by poor compliance with treatment, severe hypertriglyceridaemia and pancreatitis. CASE REPORT: The patient presented at 6 weeks' gestation with an HbA(1c) of 140 mmol/mol (15%), cholesterol 8.1 mmol/l and triglycerides 20.1 mmol/l. She wished to continue the pregnancy so lipid-lowering therapy was discontinued. She was severely insulin resistant and poorly compliant with diet and medication. A continuous subcutaneous insulin infusion was required for efficient delivery of large doses of basal insulin, alongside injected mealtime boluses, (up to 300 units insulin per day). At 17 weeks' gestation she developed acute pancreatitis secondary to hypertriglyceridaemia (triglycerides > 100 mmol/l) and required plasmapheresis. Lipid-lowering therapy was reinstated in the third trimester and plasmapheresis was required repeatedly to maintain triglycerides < 10 mmol/l. Delivery was arranged at 32 weeks, because of deteriorating glycaemic and lipid control (blood pressure was normal). Following betamethasone for fetal lung maturation, 20 units/h of intravenous insulin were required to maintain glycaemic control. A baby boy with significant subsequent developmental delay was delivered. DISCUSSION: The features of PPARG mutations are discussed, with literature on lipodystrophy and pancreatitis in pregnancy reviewed. There are few documented cases of pregnancy in women with PPARG mutations. The notable features of this case include the consequences of non-concordance with treatment, the use of continuous subcutaneous insulin infusion to treat insulin-resistant diabetes and the need for repeated plasmapheresis during pregnancy to avert pancreatitis.

Prevalence of impaired awareness of hypoglycaemia in adults with Type 1 diabetes.

AIMS: Impaired awareness of hypoglycaemia (IAH) is thought to affect approximately 25% of people with Type 1 diabetes. While this estimate was based on retrospective information from patients in several small studies performed several years ago, validated methods of assessment have not been used in a large hospital clinic-based population to ascertain the prevalence in the present era. METHODS: Five hundred and eighteen people with Type 1 diabetes were recruited by random selection over a 2-year period. Participants completed a questionnaire documenting baseline characteristics and assessment of their awareness status using the method described by Gold et al. The number of episodes of severe hypoglycaemia they had experienced in the preceding year was recorded retrospectively. RESULTS: IAH was present in 19.5% of the cohort. Compared to those with normal awareness of hypoglycaemia, those with IAH were significantly older [mean +/- standard deviation (sd); 39.3 +/- 12.9 vs. 45.9 +/- 13.5 years, P < 0.001], had a longer duration of diabetes [median (interquartile range) 14 (8-22) vs. 23 (14-32) years, P < 0.001], and had a six-fold higher frequency of severe hypoglycaemia in the previous year [0.38 +/- 1.04 (25th-75th centile 0-0) vs. 2.36 +/- 4.81 (25th-75th centile 0-2) episodes per person, P < 0.001]. CONCLUSIONS: The present survey of a large hospital-based clinic population has confirmed that a significant proportion of people with Type 1 diabetes (19.5%) continue to have IAH. Despite improvements in insulin therapies, intensification of insulin regimens and innovative patient education, the prevalence of IAH remains high in Type 1 diabetes.

An audit of the management of childhood-onset growth hormone deficiency during young adulthood in Scotland.

BACKGROUND: Adolescents with childhood onset growth hormone deficiency (CO-GHD) require re-evaluation of their growth hormone (GH) axis on attainment of final height to determine eligibility for adult GH therapy (rhGH). AIM: Retrospective multicentre review of management of young adults with CO-GHD in four paediatric centres in Scotland during transition. PATIENTS: Medical records of 130 eligible CO-GHD adolescents (78 males), who attained final height between 2005 and 2013 were reviewed. Median (range) age at initial diagnosis of CO-GHD was 10.7 years (0.1-16.4) with a stimulated GH peak of 2.3 µg/l (0.1-6.5). Median age at initiation of rhGH was 10.8 years (0.4-17.0). RESULTS: Of the 130 CO-GHD adolescents, 74/130(57 %) had GH axis re-evaluation by stimulation tests /IGF-1 measurements. Of those, 61/74 (82 %) remained GHD with 51/74 (69 %) restarting adult rhGH. Predictors of persistent GHD included an organic hypothalamic-pituitary disorder and multiple pituitary hormone deficiencies (MPHD). Of the remaining 56/130 (43 %) patients who were not re-tested, 34/56 (61 %) were transferred to adult services on rhGH without biochemical retesting and 32/34 of these had MPHD. The proportion of adults who were offered rhGH without biochemical re-testing in the four centres ranged between 10 and 50 % of their total cohort. CONCLUSIONS: A substantial proportion of adults with CO-GHD remain GHD, particularly those with MPHD and most opt for treatment with rhGH. Despite clinical guidelines, there is significant variation in the management of CO-GHD in young adulthood across Scotland.

Serum angiotensin-converting enzyme and frequency of severe hypoglycaemia in Type 1 diabetes: does a relationship exist?

AIMS: An association has been described between elevated serum angiotensin-converting enzyme (ACE) and an increased risk of severe hypoglycaemia (SH). To ascertain whether this reported association could be replicated in a different country, it was re-examined in 300 individuals with Type 1 diabetes. METHODS: People with Type 1 diabetes, none of whom was taking renin-angiotensin system blocking drugs, were recruited. Participants recorded the frequency with which they had experienced SH. Glycated haemoglobin (HbA(1c)) and serum ACE were measured. The difference in the incidence of SH between different quartiles of ACE activity and the relationship between serum ACE and SH were examined using non-parametric statistical tests and a negative binomial model. RESULTS: Data were obtained from 300 patients [158 male; HbA(1c) median (range) 8.2% (5.2-12.8%), median age 36 years (16-88); duration of diabetes 14.5 years (2-49)]. The incidence of SH was 0.93 episodes per patient year. The mean incidence of SH in the top and bottom quartiles of ACE activity was 0.5 and 1.7 episodes per patient year, respectively, but this difference was not statistically significant (P = 0.075). Spearman's test showed a very weak, although statistically significant, association between serum ACE level and SH incidence (r = 0.115, P = 0.047). The binomial model also showed a statistically significant (P = 0.002), but clinically weak, relationship between serum ACE and SH. CONCLUSIONS: The present survey showed a weak relationship between serum ACE and the frequency of SH, the clinical relevance of which is unclear. This limits the proposed role for serum ACE as an index of risk for SH.

The effects of acute hypoglycaemia on memory acquisition and recall and prospective memory in type 1 diabetes.

AIMS/HYPOTHESIS: Global memory performance is impaired during acute hypoglycaemia. This study assessed whether moderate hypoglycaemia disrupts learning and recall in isolation, and utilised a novel test of prospective memory which may better reflect the role of memory in daily life than conventional tests. SUBJECTS AND METHODS: Thirty-six subjects with type 1 diabetes participated, 20 with normal hypoglycaemia awareness (NHA) and 16 with impaired hypoglycaemia awareness (IHA). Each underwent a hypoglycaemic clamp with target blood glucose 2.5 mmol/l. Prior to hypoglycaemia, subjects attempted to memorise instructions for a prospective memory task, and recall was assessed during hypoglycaemia. Subjects then completed the learning and immediate recall stages of three conventional memory tasks (word recall, story recall, visual recall) during hypoglycaemia. Euglycaemia was restored and delayed memory for the conventional tasks was tested. The same procedures were completed in euglycaemic control studies (blood glucose 4.5 mmol/l). RESULTS: Hypoglycaemia impaired performance significantly on the prospective memory task (p = 0.004). Hypoglycaemia also significantly impaired both immediate and delayed recall for the word and story recall tasks (p < 0.01 in each case). There was no significant deterioration of performance on the visual memory task. The effect of hypoglycaemia did not differ significantly between subjects with NHA and IHA. CONCLUSIONS/INTERPRETATION: Impaired performance on the prospective memory task during hypoglycaemia demonstrates that recall is disrupted by hypoglycaemia. Impaired performance on the conventional memory tasks demonstrates that learning is also disrupted by hypoglycaemia. Results of the prospective memory task support the relevance of these findings to the everyday lives of people with diabetes.