Nicola N. Zammitt

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.

Delayed Recovery of Cognitive Function Following Hypoglycemia in Adults With Type 1 Diabetes: Effect of Impaired Awareness of Hypoglycemia

OBJECTIVE—Recovery times of cognitive functions were examined after exposure to hypoglycemia in people with diabetes with and without impaired hypoglycemia awareness. RESEARCH DESIGN AND METHODS—A total of 36 subjects with type 1 diabetes were studied (20 with normal hypoglycemia awareness [NHA] and 16 with impaired hypoglycemia awareness [IHA]). A hyperinsulinemic glucose clamp was used to lower blood glucose to 2.5 mmol/l (45 mg/dl) (hypoglycemia) for 1 h or to maintain blood glucose at 4.5 mmol/l (81 mg/dl) (euglycemia) on separate occasions. Cognitive tests were applied during each experimental condition and were repeated at 10- to 15-min intervals for 90 min after euglycemia had been restored. RESULTS—In the NHA group, performance was impaired on all cognitive tasks during hypoglycemia and remained impaired for up to 75 min on the choice reaction time (CRT) task (P = 0.03, η2 = 0.237). In the IHA group, performance did not deteriorate significantly during hypoglycemia. When all subjects were analyzed within the same general linear model, performance was impaired during hypoglycemia on all tasks. Significant impairment during recovery persisted for up to 40 min on the CRT task (P = 0.04, η2 = 0.125) with a significant glycemia-awareness interaction for CRT after one hour of hypoglycemia (P = 0.045, η2 = 0.124). Performance on the trail-making B task was impaired for up to 10 min after euglycemia was restored (P = 0.024, η2 = 0.158). CONCLUSIONS—Following hypoglycemia, the recovery time for different cognitive tasks varied considerably. In the IHA group, performance was not significantly impaired during hypoglycemia. The state of awareness of hypoglycemia may influence cognitive function during and after hypoglycemia.

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.

Flash Glucose Monitoring Improves Outcomes in a Type 1 Diabetes Clinic

The Freestyle Libre flash glucose monitoring (FGM; Abbott Diabetes Care, Witney, UK) system was introduced in the United Kingdom in 2013. Although similar to conventional continuous glucose monitoring (CGM) systems, a few significant differences exist. FGM sensors are factory calibrated and therefore do not require calibration with blood glucose testing over their 14-day lifespan. FGM is also considerably cheaper than conventional CGM but lacks alarm features and connectivity with continuous subcutaneous insulin infusion (CSII) devices, such as low-glucose suspend. The accuracy and usability of FGM have been validated in patients with both type 1 and type 2 diabetes. We sought to prospectively assess the impact of introducing FGM to patients attending our type 1 diabetes clinic in a university teaching hospital, over a 16-week period. In particular, we assessed the impact on HbA1c, hypoglycemia (recorded and self-reported) and quality of life measures (Diabetes Distress Scale). The only inclusion criteria were a diagnosis of type 1 diabetes and a willingness to upload FGM data at least monthly. Data were analyzed as intention-to-treat. Of the 25 participants, 13 were men, and the mean age was 39.8 ± 2.0 years. Mean duration of diabetes was 19 ± 2 years. A total of 8 patients were treated with CSII, and 17 used multiple daily injections. Immediately prior to commencement of FGM, the mean HbA1c of participants was 8.0 ± 0.14%, which did not differ from the mean of the previous 4 clinic recorded HbA1c values (8.0 ± 0.2%, P = .833). Mean HbA1c fell from 8.0 ± 0.14% to 7.5 ± 0.14% (–0.48%, P = .001) following 16 weeks of FGM. The number of people with an HbA1c of 7.5% or below more than doubled after FGM use (Figure 1). The mean reduction in HbA1c was greater in those with a baseline HbA1c > 7.5%: –0.59 ± 0.15% compared to −0.2 ± 0.11% in those with HbA1c <7.5% at baseline (P = .005). Female participants had greater mean reduction in HbA1c (–0.74 ± 0.19%) compared to men (–0.23 ± 0.15%, P = .049) despite no significant difference in baseline HbA1c (8.2 ± 0.25% vs 7.8 ± 0.14%, P = .174). Of participants, 24% (6/25) achieved an HbA1c reduction of greater than 1.0%. Episodes of hypoglycemia (glucose <72 mg/dl), as determined from FGM glucose data, reduced from 17 (IQR 10-20) in the first 2 weeks of use to 12 (IQR 8.5-16) in the final 2 weeks (P = .019). Significant reductions were observed in the Diabetes Distress Scale mean score (P = .006), as well as emotional burden (P = .035) and regimen-related distress subscores (P = .005). FGM use was associated with a significant increase in delivering bolus insulin 15-20 minutes in advance of meals (compared to immediately before or after meals), from 16% to 44% (P = .026). In summary, these results support the wider use of FGM to improve outcomes in people with type 1 diabetes. Benefits are realized across a number of important domains including improved HbA1c, hypoglycemia, and quality of life. 661560 DSTXXX10.1177/1932296816661560Journal of Diabetes Science and TechnologyDover et al letter2016

Modeling the consistency of hypoglycemic symptoms: high variability in diabetes.

BACKGROUND The aim of the present study was to examine symptoms of hypoglycemia, to develop a method to quantify individual differences in the consistency of symptom reporting, and to investigate which factors affect these differences. METHODS Participants recorded their symptoms with every episode of hypoglycemia over a 9-12-month period. A novel logistic-type latent variable model was developed to quantify the consistency of each individuals symptom complex and was used to analyze data from 59 subjects (median age, 57.5 years [range, 22-74 years], 65% male, 77% type 1 diabetes) who had experienced 19 or more hypoglycemic episodes. The association between the calculated consistency parameter and age, sex, type and duration of diabetes, and C-peptide and serum angiotensin converting enzyme concentration was examined using a generalized linear model. Analyses were performed under a Bayesian framework, using Markov chain Monte-Carlo methodology. RESULTS Individuals exhibited substantial differences in between-episode consistency of their symptom reports, with only a small number of individuals exhibiting high levels of consistency. Men were more consistent than women. No other factors affected consistency in patients with normal hypoglycemia awareness. CONCLUSIONS By using a novel stochastic model as a quantitative tool to compare the consistency of hypoglycemic symptom reporting, much greater intra-individual variability in symptom reporting was identified than has been recognized previously. This is relevant when instructing patients on identification of hypoglycemic symptoms and in interpreting symptomatic responses during experimentally induced hypoglycemia.

Optimal Glycaemic Control in Elderly People with Type 2 Diabetes: What Does the Evidence Say?

The global prevalence of type 2 diabetes mellitus (T2DM) is rising in an ageing population through a combination of lifestyle changes and greater longevity. However, by excluding participants aged over 70 years, most major interventional trials on which current diabetes therapeutic guidelines are based have failed to provide specific evidence to support the prescribed management of diabetes in elderly people. While diabetes per se has a significant impact on the elderly person, the side effects of medications, particularly hypoglycaemia, prevent optimisation of diabetes treatment. Hypoglycaemia is associated with significant morbidity, to which elderly people are often more vulnerable because of factors such as the effects of ageing, progressive renal impairment, frailty, polypharmacy and cognitive decline. T2DM is associated with accelerated cognitive decline in some individuals, and recurrent severe hypoglycaemia has been implicated as a potential contributory factor. Although the evidence for selection of appropriate glycaemic targets in elderly patients is sparse, it is now acknowledged that prevention of hypoglycaemia must influence individualisation of treatment goals in this vulnerable group. This should also be reflected by the choice of anti-diabetes agents that are initiated when diet and lifestyle advice is ineffective. Recently developed international guidelines, which have specifically addressed the management of diabetes in elderly people, highlight the importance of a pragmatic management approach rather than attempting to achieve a generic glycated haemoglobin goal and are summarised in this article.

Effects of Acute Hypoglycemia on Working Memory and Language Processing in Adults With and Without Type 1 Diabetes

OBJECTIVE To examine the effects of hypoglycemia on language processing in adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS Forty adults were studied (20 with type 1 diabetes and 20 healthy volunteers) using a hyperinsulinemic glucose clamp to lower blood glucose to 2.5 mmol/L (45 mg/dL) (hypoglycemia) for 60 min, or to maintain blood glucose at 4.5 mmol/L (81 mg/dL) (euglycemia), on separate occasions. Language tests were applied to assess the effects of hypoglycemia on the relationship between working memory and language (reading span), grammatical decoding (self-paced reading), and grammatical encoding (subject-verb agreement). RESULTS Hypoglycemia caused a significant deterioration in reading span (P < 0.001; η2 = 0.37; Cohen d = 0.65) and a fall in correct responses (P = 0.005; η2 = 0.19; Cohen d = 0.41). On the self-paced reading test, the reading time for the first sentence fragment increased during hypoglycemia (P = 0.039; η2 = 0.11; Cohen d = 0.25). For the reading of the next fragment, hypoglycemia affected the healthy volunteer group more than the adults with type 1 diabetes (P = 0.03; η2 = 0.12; Cohen d = 0.25). However, hypoglycemia did not significantly affect the number of errors in sentence comprehension or the time taken to answer questions. Hypoglycemia caused a deterioration of subject-verb agreement (correct responses: P = 0.011; η2 = 0.159; Cohen d = 0.31). CONCLUSIONS Hypoglycemia caused a significant deterioration in reading span and in the accuracy of subject-verb agreement, both of which are practical aspects of language involved in its everyday use. Language processing is therefore impaired during moderate hypoglycemia.

Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes

OBJECTIVE To ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. RESEARCH DESIGN AND METHODS Fourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. RESULTS Cognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non–sleep-deprived conditions. However, in the sleep-deprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P < 0.001) and hypoglycemia symptom scores were significantly higher (P < 0.001), even when symptoms that may have been caused by sleep deprivation, such as tiredness, were removed. CONCLUSIONS Hypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period.

The prevalence of structural pituitary abnormalities by MRI scanning in men presenting with isolated hypogonadotrophic hypogonadism

Hypogonadotrophic hypogonadism (HH) is commonly associated with ageing, obesity and type 2 diabetes. The indications for pituitary imaging are controversial, and current guidelines are based on small case series.

Predicting outcomes and complications following radioiodine therapy in Graves’ thyrotoxicosis

Radioiodine (RAI) is an effective treatment for Graves’ thyrotoxicosis but is associated with a failure rate of 15% and may be a risk factor for thyroid eye disease (TED) and weight gain. We sought to examine predictors of RAI failure, weight gain, TED and patient satisfaction.