Impact of severe hypoglycaemia on psychological outcomes in adults with Type 2 diabetes: a systematic review.

AIM: Hypoglycaemia affects many people with Type 2 diabetes using insulin and other glucose-lowering therapies. This systematic review examined the impact of severe hypoglycaemia (episodes requiring external assistance) on psychological outcomes (e.g. emotional well-being, health status and quality of life) in adults with Type 2 diabetes. METHODS: MEDLINE Complete, PsycINFO and CINAHL databases were searched for peer-reviewed empirical studies, published in English, reporting the occurrence and severity of hypoglycaemia and its relationship with patient-reported outcomes (PROs) in adults with Type 2 diabetes. Data were extracted from published reports and analysed. RESULTS: Of 3756 potentially relevant abstracts, 29 studies met the inclusion criteria. Most reported cross-sectional data and sample sizes varied widely (N = 71 to 17 563). Although definitions of mild and severe hypoglycaemia were largely consistent between studies, additional non-standard categorizations (e.g. moderate, very severe) were apparent and recall periods varied. Overall, severe hypoglycaemia was associated with increased fear of hypoglycaemia and decreased emotional well-being, health status and diabetes-specific quality of life. Effect sizes show that the association with fear of hypoglycaemia was stronger than with general health status. CONCLUSIONS: Notwithstanding the limitations of the empirical studies, these findings indicate that severe hypoglycaemia in adults with Type 2 diabetes (insulin- and non-insulin-treated) is associated with impaired psychological outcomes. Healthcare professionals should address the psychological impact of severe hypoglycaemia during clinical consultations, to support individuals to minimize exposure to, and the psychological consequences of, severe hypoglycaemia.

Hypoglycaemia in adults with insulin-treated diabetes in the UK: self-reported frequency and effects.

AIM: Few real-life studies of non-severe (self-treated) hypoglycaemic events are available. This survey quantified the self-reported frequency of non-severe hypoglycaemia and its effects in adults with insulin-treated diabetes in the UK. METHODS: Adults aged > 15 years with Type 1 diabetes or insulin-treated Type 2 diabetes completed ≤ 4 weekly questionnaires (7-day recall). Respondents with Type 2 diabetes were grouped by insulin regimen: basal-only, basal-bolus and 'other'. RESULTS: Overall, 1038 respondents (466 with Type 1 diabetes, 572 with Type 2 diabetes) completed 3528 questionnaires. Mean numbers of non-severe events per week were 2.4 (Type 1 diabetes; median = 2) and 0.8 (Type 2 diabetes; median = 0); 23% and 26% of non-severe events occurred at night, respectively. Fatigue and reduced alertness were the commonest issues following events (78% and 51% of respondents, respectively). The effects of nocturnal events persisted longer than those of daytime events: Type 1 diabetes = 10.6 vs. 4.9 h (P = 0.0002); Type 2 diabetes = 15.3 vs. 5.1 h (P < 0.0001). In the week following an event, respondents' blood glucose measurements increased by 4.3 (Type 1 diabetes; 12% increment) and 4.2 (Type 2 diabetes; 21% increment) tests/week. In employed respondents, 20% of events caused work-time loss, more so following nocturnal (vs. daytime) hypoglycaemia: Type 1 diabetes = 2.7 vs. 1.1 h (P = 0.0184); Type 2 diabetes = 2.5 vs. 1.6 h (P = 0.1340). Most respondents rarely/never informed healthcare professionals about events (Type 1 diabetes = 82%, Type 2 diabetes = 69%). CONCLUSIONS: Non-severe hypoglycaemia is common in adults with insulin-treated diabetes in the UK, with consequent health-related/economic effects. Communication about non-severe hypoglycaemia is limited and the burden of hypoglycaemia may be underestimated.

Severe hypoglycaemia in adults with insulin-treated diabetes: impact on healthcare resources.

AIMS: To assess resource utilization associated with severe hypoglycaemia across three insulin regimens in a large phase 3a clinical programme involving people with Type 1 diabetes treated with basal-bolus insulin, people with Type 2 diabetes treated with multiple daily injections and people with Type 2 diabetes treated with basal-oral therapy. METHODS: Data relating to severe hypoglycaemia events (defined as episodes requiring external assistance) from the insulin degludec and insulin degludec/insulin aspart programme (15 trials) were analysed using descriptive statistics. Comparators included insulin glargine, biphasic insulin aspart, insulin detemir and sitagliptin. Mealtime insulin aspart was used in some regimens. This analysis used the serious adverse events records, which documented the use of ambulance/emergency teams, a hospital/emergency room visit ≤ 24 h, or a hospital visit > 24 h. RESULTS: In total, 536 severe hypoglycaemia events were analysed, of which 157 (29.3%) involved an ambulance/emergency team, 64 (11.9%) led to hospital/emergency room attendance of ≤ 24 h and 36 (6.7%) required hospital admission (> 24 h). Although there were fewer events in people with Type 2 diabetes compared with Type 1 diabetes, once a severe episode occurred, the tendency to utilize healthcare resources was higher in Type 2 diabetes vs. Type 1 diabetes. A higher proportion (47.6%) in the basal-oral therapy group required hospital treatment for > 24 h versus the Type 1 diabetes (5.0%) and Type 2 diabetes multiple daily injections (5.3%) groups. CONCLUSION: This analysis suggests that severe hypoglycaemia events often result in emergency/ambulance calls and hospital treatment, incurring a substantial health economic burden, and were associated with all insulin regimens.

Characterizing problematic hypoglycaemia: iterative design and preliminary psychometric validation of the Hypoglycaemia Awareness Questionnaire (HypoA-Q).

AIMS: To design and conduct preliminary validation of a measure of hypoglycaemia awareness and problematic hypoglycaemia, the Hypoglycaemia Awareness Questionnaire. METHODS: Exploratory and cognitive debriefing interviews were conducted with 17 adults (nine of whom were women) with Type 1 diabetes (mean ± sd age 48 ± 10 years). Questionnaire items were modified in consultation with diabetologists/psychologists. Psychometric validation was undertaken using data from 120 adults (53 women) with Type 1 diabetes (mean ± sd age 44 ± 16 years; 50% with clinically diagnosed impaired awareness of hypoglycaemia), who completed the following questionnaires: the Hypoglycaemia Awareness Questionnaire, the Gold score, the Clarke questionnaire and the Problem Areas in Diabetes questionnaire. RESULTS: Iterative design resulted in 33 items eliciting responses about awareness of hypoglycaemia when awake/asleep and hypoglycaemia frequency, severity and impact (healthcare utilization). Psychometric analysis identified three subscales reflecting 'impaired awareness', 'symptom level' and 'symptom frequency'. Convergent validity was indicated by strong correlations between the 'impaired awareness' subscale and existing measures of awareness: (Gold: rs =0.75, P < 0.01; Clarke: rs =0.76, P < 0.01). Divergent validity was indicated by weaker correlations with diabetes-related distress (Problem Areas in Diabetes: rs =0.25, P < 0.01) and HbA1c (rs =-0.05, non-significant). The 'impaired awareness' subscale and other items discriminated between those with impaired and intact awareness (Gold score). The 'impaired awareness' subscale and other items contributed significantly to models explaining the occurrence of severe hypoglycaemia and hypoglycaemia when asleep. CONCLUSIONS: This preliminary validation shows the Hypoglycaemia Awareness Questionnaire has robust face and content validity; satisfactory structure; internal reliability; convergent, divergent and known groups validity. The impaired awareness subscale and other items contribute significantly to models explaining recall of severe and nocturnal hypoglycaemia. Prospective validation, including determination of a threshold to identify impaired awareness, is now warranted.

Effects of sitagliptin on counter-regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double-blind placebo-controlled crossover study.

AIMS: To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes. METHODS: We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction. RESULTS: Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008]. CONCLUSIONS: Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia.

Hypoglycaemia symptoms and impaired awareness of hypoglycaemia in adults with Type 1 diabetes: the association with diabetes duration.

AIMS: To examine the association between diabetes duration and hypoglycaemia symptom profiles and the presence of impaired awareness of hypoglycaemia. METHODS: A cross-sectional study was performed, using validated methods for recording hypoglycaemia symptoms and assessing hypoglycaemia awareness. The associations between symptom intensity, hypoglycaemia awareness and diabetes duration were examined, and the prevalence of impaired awareness was ascertained for Type 1 diabetes of differing durations. RESULTS: Questionnaires were mailed to 636 adults with Type 1 diabetes, of whom 445 (70%) returned them. A total of 440 completed questionnaires were suitable for analysis. Longer diabetes duration was associated with lower intensity of autonomic symptoms (P for trend <0.001), but no association was observed with neuroglycopenic symptoms. The overall prevalence of impaired awareness of hypoglycaemia in this cohort was 17% (95% CI 14-21%) and increased with diabetes duration, from 3% for duration 2-9 years to 28% for duration ≥30 years (P for trend <0.001). Low autonomic symptom scores were not associated with a higher prevalence of impaired awareness. CONCLUSIONS: Longer diabetes duration was associated with lower intensity of autonomic symptoms and a higher prevalence of impaired awareness of hypoglycaemia, suggesting that subjective symptoms of hypoglycaemia change over time. These observations underline the need for regular patient education about hypoglycaemia symptomatology and clinical screening for impaired awareness of hypoglycaemia.

Diabetes and driving.

The principal safety concern for driving for people treated with insulin or insulin secretagogues is hypoglycaemia, which impairs driving performance. Other complications, such as those causing visual impairment and peripheral neuropathy, are also relevant to medical fitness to drive. Case control studies have suggested that drivers with diabetes pose a modestly increased but acceptable and measurable risk of motor vehicle accidents compared to non-diabetic drivers, but many studies are limited and of poor quality. Factors which have been shown to increase driving risk include previous episodes of severe hypoglycaemia, previous hypoglycaemia while driving, strict glycaemic control (lower HbA1c) and absence of blood glucose monitoring before driving. Impaired awareness of hypoglycaemia may be counteracted by frequent blood glucose testing. The European Union Third directive on driving (2006) has necessitated changes in statutory regulations for driving licences for people with diabetes in all European States, including the UK. Stricter criteria have been introduced for Group 1 vehicle licences while those for Group 2 licences have been relaxed. Insulin-treated drivers can now apply to drive Group 2 vehicles, but in the UK must meet very strict criteria and be assessed by an independent specialist to be issued with a 1-year licence.

A comparison of insulin detemir and neutral protamine Hagedorn (isophane) insulin in the treatment of diabetes: a systematic review.

The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.

Hypoglycaemia and accident risk in people with type 2 diabetes mellitus treated with non-insulin antidiabetes drugs.

AIMS: To assess associations between hypoglycaemia and risk of accidents resulting in hospital visits among people with type 2 diabetes receiving antidiabetes drugs without insulin. METHODS: People with type 2 diabetes who were not treated with insulin were identified from a US-based employer claims database (1998-2010). Following initiation of an antidiabetes drug, the occurrence of accidents resulting in hospital visits was compared between people with, and without, claims for hypoglycaemia using multivariable Cox proportional hazard models adjusted for demographics, comorbidities, prior treatments and prior medical service use. Additional analyses were stratified by age 65 years or older. RESULTS: A total of N = 5582 people with claims for hypoglycaemia and N = 27,910 with no such claims were included. Accidents resulting in hospital visits occurred in 5.5 and 2.8% of people with, and without, hypoglycaemia, respectively. After adjusting for baseline characteristics, hypoglycaemia was associated with significantly increased hazards for any accident [hazard ratio (HR) 1.39, 95% CI 1.21-1.59, p < 0.001], accidental falls (HR 1.36, 95% CI 1.13-1.65, p < 0.001) and motor vehicle accidents (HR 1.82, 95% CI 1.18-2.80, p = 0.007). In age-stratified analyses, hypoglycaemia was associated with greater hazards of driving-related accidents in people younger than age 65 and falls in people aged 65 or older. CONCLUSIONS: In people with type 2 diabetes receiving antidiabetes drugs without insulin, hypoglycaemia was associated with a significantly higher risk of accidents resulting in hospital visits, including accidents related to driving and falls.

The impact of hypoglycaemia on quality of life and related patient-reported outcomes in Type 2 diabetes: a narrative review.

As a common side effect of insulin treatment for diabetes, hypoglycaemia is a constant threat and can have far-reaching and potentially devastating consequences, including immediate physical injury as well as more pervasive cognitive, behavioural and emotional effects. Moreover, as a significant limiting factor in achieving optimal glycaemic control, exposure to hypoglycaemia can influence diabetes self-management. Although hypoglycaemia is known to occur in Type 2 diabetes, its morbidity and impact on the individual are not well recognized. The aim of the current review is to examine published evidence to achieve a synthesis of the scope and significance of the potential detriment caused by hypoglycaemia to individuals with Type 2 diabetes. The implications of these observations for treatment and research have also been considered. A narrative review was performed of empirical papers published in English since 1966, reporting the effect of hypoglycaemia on quality of life and related outcomes (including generic and diabetes-specific quality of life, emotional well-being and health utilities) in Type 2 diabetes. Research demonstrates the potential impact of hypoglycaemia on the lives of people with Type 2 diabetes, from an association with depressive symptoms and heightened anxiety, to impairment of the ability to drive, work and function in ways that are important for quality of life. Few studies consider hypoglycaemia as an explanatory variable in combination with quality of life or related primary endpoints. As a consequence, there is a pressing need for high-quality research into the overall impact of hypoglycaemia on the lives of people with Type 2 diabetes.

Does severe hypoglycaemia influence microvascular complications in Type 1 diabetes? An analysis of the Diabetes Control and Complications Trial database.

AIMS: Severe hypoglycaemia may have a role in aggravating micro- and macrovascular disease in diabetes. Data from the Diabetes Control and Complication Trial have been reanalysed to ascertain whether the frequency of severe hypoglycaemia exerted an influence on the development and progression of retinopathy or nephropathy in people with Type 1 diabetes. METHODS: Using binary longitudinal multiple logistic regression, HbA(1c) at study baseline, mean HbA(1c) throughout the study and the number of severe hypoglycaemic episodes during the trial were compared to examine the risk of development/progression of retinopathy and nephropathy. RESULTS: Average HbA(1c) during the study and/or HbA(1c) at baseline were independently predictive of retinopathy and nephropathy both in the intensively and the conventionally treated patients (all P ≤ 0.001). However, the number of hypoglycaemic episodes did not add to HbA(1c) in predicting retinopathy [odds ratio (95% CI) 0.99 (0.96-1.01), P = 0.51 in intensively treated patients, 0.94 (0.89-1.00), P = 0.05, conventional] or nephropathy [odds ratio (95% CI) 0.98 (0.95-1.01), P = 0.48 intensive, 1.03 (0.98-1.10), P = 0.17 conventional]. CONCLUSIONS: The frequency of exposure to severe hypoglycaemia did not predict a different risk of developing retinopathy or nephropathy in either treatment group of the Diabetes Control and Complications Trial at any given HbA(1c) .

Prevalence of abnormal plasma liver enzymes in older people with Type 2 diabetes.

AIMS: To determine the prevalence and distribution of abnormal plasma liver enzymes in a representative sample of older adults with Type 2 diabetes. METHODS: Plasma concentrations of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase were measured in a randomly selected, population-based cohort of 1066 men and women aged 60-75 years with Type 2 diabetes (the Edinburgh Type 2 Diabetes Study). RESULTS: Overall, 29.1% (95% CI 26.1-31.8) of patients had one or more plasma liver enzymes above the upper limit of the normal reference range. Only 10.1% of these patients had a prior history of liver disease and a further 12.4% reported alcohol intake above recommended limits. Alanine aminotransferase was the most commonly raised liver enzyme (23.1% of patients). The prevalence of abnormal liver enzymes was significantly higher in men (odds ratio 1.40, 95% CI 1.07-1.83), in the youngest 5-year age band (odds ratio 2.02, 95% CI 1.44-2.84), in patients with diabetes duration < 5 years (odds ratio 1.38, 95% CI 1.01-1.90), plasma HbA(1c) ≥ 58 mmol/mol (7.5%) (odds ratio 1.43, 95% CI 1.09-1.88), obese BMI (odds ratio 2.84, 95% CI 1.59-3.06) and secondary care management for their diabetes (odds ratio 1.40, 95% CI 1.05-1.87). However, all these factors combined accounted for only 7.6% of the variation in liver enzyme abnormality. CONCLUSIONS: The prevalence of elevated liver enzymes in people with Type 2 diabetes is high, with only modest variation between clinically defined patient groups. Further research is required to determine the prognostic value of raised, routinely measured liver enzymes to inform decisions on appropriate follow-up investigations.

Severe hypoglycaemia and late-life cognitive ability in older people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study.

OBJECTIVE: To determine the association between lifetime severe hypoglycaemia and late-life cognitive ability in older people with Type 2 diabetes. METHODS: Cross-sectional, population-based study of 1066 men and women aged 60-75 years, with Type 2 diabetes. Frequency of severe hypoglycaemia over a person's lifetime and in the year prior to cognitive testing was assessed using a previously validated self-completion questionnaire. Results of age-sensitive neuropsychological tests were combined to derive a late-life general cognitive ability factor, 'g'. Vocabulary test scores, which are stable during ageing, were used to estimate early life (prior) cognitive ability. RESULTS: After age- and sex- adjustment, 'g' was lower in subjects reporting at least one prior severe hypoglycaemia episode (n = 113), compared with those who did not report severe hypoglycaemia (mean 'g'-0.34 vs. 0.05, P < 0.001). Mean vocabulary test scores did not differ significantly between the two groups (30.2 vs. 31.0, P = 0.13). After adjustment for vocabulary, difference in 'g' between the groups persisted (means -0.25 vs. 0.04, P < 0.001), with the group with severe hypoglycaemia demonstrating poorer performance on tests of Verbal Fluency (34.5 vs. 37.3, P = 0.02), Digit Symbol Testing (45.9 vs. 49.9, P = 0.002), Letter-Number Sequencing (9.1 vs. 9.8, P = 0.005) and Trail Making (P < 0.001). These associations persisted after adjustment for duration of diabetes, vascular disease and other potential confounders. CONCLUSIONS: Self-reported history of severe hypoglycaemia was associated with poorer late-life cognitive ability in people with Type 2 diabetes. Persistence of this association after adjustment for estimated prior cognitive ability suggests that the association may be attributable, at least in part, to an effect of hypoglycaemia on age-related cognitive decline.

Cognitive functioning in type 1 diabetes: the Diabetes Control and Complications Trial (DCCT) revisited.

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study has allowed an examination of the long-term effects of type 1 diabetes and intensity of treatment on cognitive function. The association observed between chronic hyperglycaemia and mild cognitive dysfunction, affecting motor speed and psychomotor efficiency, has been re-evaluated by Jacobson et al. (Diabetologia doi: 10.1007/s00125-010-1883-9) to determine the possible contribution of macrovascular risk factors, subclinical macrovascular disease and microvascular complications (retinopathy and nephropathy). This has revealed associations between mild impairment of psychomotor efficiency and hypertension, glycaemic control and the presence of retinopathy and nephropathy, while smoking history was associated with modest abnormalities in several cognitive domains. Neither macrovascular risk factors nor a history of severe hypoglycaemia was associated with the cognitive decrements; cerebral microangiopathy has been proposed as a possible underlying cause. Although the degree of cognitive impairment was mild and limited to a few domains, these decrements may influence the performance of everyday activities, such as driving.

Frequency of symptomatic and asymptomatic hypoglycaemia in Type 1 diabetes: effect of impaired awareness of hypoglycaemia.

AIMS: To characterize the frequency and the nature (symptomatic vs. asymptomatic) of hypoglycaemia in people with Type 1 diabetes with impaired awareness of hypoglycaemia. METHODS: A group of 19 patients with Type 1 diabetes with normal hypoglycaemia awareness were matched for age, sex, duration of diabetes and glycaemic control with 19 patients with impaired awareness of hypoglycaemia. Frequency of severe hypoglycaemia in the preceding year was estimated retrospectively. Capillary blood glucose was monitored prospectively four times daily, over a 4-week period. All blood glucose values < 3 mmol/l were recorded and classified by symptom response. RESULTS: The patients with impaired awareness of hypoglycaemia exhibited twice the frequency of all episodes of hypoglycaemia over the 4-week monitoring period than those with normal awareness (mean ±sd 7.9 ± 5.4 vs. 3.7 ± 3.6, P = 0.003). No differences between the two subgroups were observed in the total number of symptomatic hypoglycaemia episodes (4.2 ± 3.3 vs. 3.2 ± 3.4, P = 0.25). The group with impaired awareness of hypoglycaemia had a sevenfold higher incidence of asymptomatic hypoglycaemia than those with normal awareness (3.7 ± 5.3 vs. 0.5 ± 1.2, P = 0.001); these episodes comprised 47% of all glucose values < 3.0 mmol/l in this group, compared with 14% in the normal awareness group. The annual prevalence of severe hypoglycaemia for patients with impaired awareness of hypoglycaemia was 53% compared with 5% for patients with normal awareness, and these patients had a significantly higher incidence of severe events (1.6 ± 2.8 vs. 0.1 ± 0.3, P = 0.001). CONCLUSIONS: Adults with Type 1 diabetes who have impaired awareness of hypoglycaemia are exposed to a much higher incidence of asymptomatic hypoglycaemia than those with normal awareness and are at higher risk of developing severe hypoglycaemia.

The use of ultrasound to diagnose hepatic steatosis in type 2 diabetes: intra- and interobserver variability and comparison with magnetic resonance spectroscopy.

AIM: To compare ultrasound gradings of steatosis with fat fraction (FF) on magnetic resonance spectroscopy (MRS; the non-invasive reference standard for quantification of hepatic steatosis), and evaluate inter- and intraobserver variability in the ultrasound gradings. MATERIALS AND METHODS: Triple grading of hepatic ultrasound examination was performed by three independent graders on 131 people with type 2 diabetes. The stored images of 60 of these individuals were assessed twice by each grader on separate occasions. Fifty-eight patients were pre-selected on the basis of ultrasound grading (normal, indeterminate/mild steatosis, or severe steatosis) to undergo (1)H-MRS. The sensitivity and specificity of the ultrasound gradings were determined with reference to MRS data, using two cut-offs of FF to define steatosis, ≥9% and ≥6.1%. RESULTS: Median (intraquartile range) MRS FF (%) in the participants graded on ultrasound as normal, indeterminate/mild steatosis, and severe steatosis were 4.2 (1.2-5.7), 4.1 (3.1-8.5) and 19.4 (12.9-27.5), respectively. Using a liver FF of ≥6.1% on MRS to denote hepatic steatosis, the unadjusted sensitivity and specificity of ultrasound gradings (severe versus other grades of steatosis) were 71 and 100%, respectively. Interobserver agreement within one grade was observed in 79% of cases. Exact intraobserver agreement ranged from 62 to 87%. CONCLUSION: Hepatic ultrasound provided a good measure of the presence of significant hepatic steatosis with good intra- and interobserver agreement. The grading of a mildly steatotic liver was less secure and, in particular, there was considerable overlap in hepatic FF with those who had a normal liver on ultrasound.

Impaired hypoglycaemia awareness and employment in people with Type 1 diabetes.

BACKGROUND: Impaired awareness of hypoglycaemia (IAH) is common in adults with Type 1 diabetes mellitus (T1DM) and is a major risk factor for severe hypoglycaemia. Little is known about its effect on employment status. AIMS: To examine the effect that IAH has on the employment status or employability of people with T1DM. METHODS: A randomly selected cohort of adults of employment age with T1DM completed a questionnaire detailing the history of their diabetes, their occupational history (including job and industry type) and assessing both their hypoglycaemia awareness status and whether in their view their ability to obtain or retain employment had been adversely affected by having diabetes. RESULTS: A total of 252 patients participated, with the following characteristics: 135 males, mean HbA1c 8.5% [standard deviation (SD) 1.4], mean age 43.3 years (SD 13.2), mean duration of diabetes 21.3 years (SD 12.8) and prevalence of IAH 23.4%. The employment rate was comparable between those with preserved awareness (73%) and the IAH group (66%) (not significant). People with IAH were older (P < 0.05) and also more commonly felt that having diabetes affected their ability to work (P < 0.05). CONCLUSIONS: This study is the first to demonstrate that those with T1DM and IAH remain as economically active as those with normal awareness of hypoglycaemia, although subjects with IAH were significantly more likely to feel that having diabetes had adversely affected their capacity for employment.

Symptoms of depression but not anxiety are associated with central obesity and cardiovascular disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: The aim of the study was to identify risk factors for depression and anxiety in a well-characterised cohort of individuals with type 2 diabetes mellitus. METHODS: We used baseline data from participants (n = 1,066, 48.7% women, aged 67.9 +/- 4.2 years) from the Edinburgh Type 2 Diabetes Study. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Obesity was characterised according to both overall (body mass index, fat mass) and abdominal (waist circumference) measurements. Cardiovascular disease was assessed by questionnaire, physical examination and review of medical records. Stepwise multiple linear regression was performed to identify explanatory variables related to either anxiety or depression HADS scores. RESULTS: Abdominal obesity (waist circumference) and cardiovascular disease (ischaemic heart disease and ankle-brachial pressure index) were related to depression but not anxiety. Lifetime history of severe hypoglycaemia was associated with anxiety. Other cardiovascular risk factors or microvascular complications were not related to either anxiety or depressive symptoms. CONCLUSIONS/INTERPRETATION: Depression but not anxiety is associated with abdominal obesity and cardiovascular disease in people with type 2 diabetes mellitus. This knowledge may help to identify depressive symptoms among patients with type 2 diabetes who are at greatest risk.