Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study.

AIMS: To ascertain the frequency and identify predictors of self-reported hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes. METHODS: A random sample of 267 people with insulin-treated diabetes were recruited from a population-based diabetes register in Tayside, Scotland. Each subject prospectively recorded the number of mild and severe hypoglycaemic episodes experienced over a 1-month period. Ordinal logistic regression was performed to identify potential predictors of hypoglycaemia. RESULTS: Five hundred and seventy-two hypoglycaemic events were reported by 155 patients. The participants with Type 1 diabetes had a total of 336 hypoglycaemic events with a rate of 42.89 events per patient per year. Of these, nine were severe hypoglycaemic events, with a rate of 1.15 events per patient per year. Participants with insulin-treated Type 2 diabetes experienced a total of 236 hypoglycaemic events with a rate of 16.37 events per patient per year. Of these, five were severe hypoglycaemic events, which would be equivalent to 0.35 events per patient per year. Predictors of hypoglycaemia in Type 1 diabetes were a history of previous hypoglycaemia (P = 0.006) and co-prescribing of any oral drug (P = 0.048). In patients with insulin-treated Type 2 diabetes, a history of previous hypoglycaemia (P < 0.0001) and duration of insulin treatment (P = 0.014) were significant predictors. CONCLUSION: The incidence of self-reported severe hypoglycaemia in insulin-treated Type 2 diabetes is lower than in Type 1 diabetes but does occur more often than previously reported and with sufficient frequency to cause significant morbidity. Duration of insulin treatment is a key predictor of hypoglycaemia in insulin-treated Type 2 diabetes.     

Lower levels of circulating IGF‐I in Type 1 diabetic women with frequent severe hypoglycaemia during pregnancy

Aims Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin‐like growth factor I (IGF‐I) levels. Methods A prospective, observational study of 107 consecutive pregnant women with Type 1 diabetes. Blood samples were drawn for IGF‐I and placental GH analyses at 8, 14, 21, 27 and 33 weeks. Severe hypoglycaemic events were reported within 24 h. Results Eleven women (10%) experienced frequent severe hypoglycaemia (≥ 5 events), accounting for 60% of all events. Throughout pregnancy, IGF‐I levels were 25% lower in these women (P < 0.005) compared with the remaining women, despite similar placental GH levels. Eighty per cent of the severe hypoglycaemic events occurred before 20 weeks when IGF‐I levels were at their lowest. This finding was not explained by differences in insulin dose, median plasma glucose levels or glycated haemoglobin. History of severe hypoglycaemia the year preceding pregnancy and impaired hypoglycaemia awareness—being the only predictors of frequent severe hypoglycaemia in a logistic regression analysis—were not associated with IGF‐I or placental GH levels at 8 weeks. Conclusions In women with Type 1 diabetes experiencing frequent severe hypoglycaemia during pregnancy, IGF‐I levels are significantly lower compared with the remaining women despite similar placental GH levels. IGF‐I levels are lowest in early pregnancy where the incidence of severe hypoglycaemia is highest. IGF‐I may be a novel factor of interest in the investigation of severe hypoglycaemia in patients with Type 1 diabetes.     

Mechanism of disopyramide‐induced hypoglycaemia in a patient with Type 2 diabetes

Background Disopyramide, an antiarrhythmia drug, has been reported to cause hypoglycaemia. Pre‐existing factors that increase the concentration of the drug in the blood increase the risk of hypoglycaemia. Furthermore, other factors can also increase the risk of hypoglycaemia even when disopyramide levels are in the therapeutic range. It has been proposed that disopyramide‐induced hypoglycaemia is caused by inhibition of the pancreatic B‐cell K_ATP channels. Case report We report a case of severe disopyramide‐induced hypoglycaemia in a 62‐year‐old woman with Type 2 diabetes taking low‐dose glimepiride treatment. She had not experienced hypoglycaemia prior to the start of disopyramide therapy. No further hypoglycaemic episodes occurred following withdrawal of disopyramide therapy. Functional study Current recordings of K_ATP channels expressed in Xenopus oocytes showed that at their estimated therapeutic concentrations, disopyramide and glimepiride inhibited K_ATP channels by about 50–60%. However, when both drugs were applied together, K_ATP channels were almost completely closed (~95%). Such dramatic inhibition of K_ATP channels is sufficient to cause B‐cell membrane depolarization and stimulate insulin secretion. Conclusions Disopyramide therapy is not recommended for patients treated with K_ATP channel inhibitors.     

Acute brain injury in hypoglycaemia-induced hemiplegia.

BACKGROUND: The development of hemiplegia as a result of hypoglycaemia was first described in 1928. However, the mechanism remains unclear. CASE REPORT: We report a case of a 58-year-old male with diabetes, who developed left hemiplegia during a severe hypoglycaemic event. Results Diffusion-weighted magnetic resonance imaging detected an increased signal intensity in the pons, indicating that the patient's hemiplegia resulted from acute brain injury. CONCLUSIONS: This report provides evidence that acute brain injury may be a cause of the neurological deficit.     

Association of hypoglycaemia severity with clinical,patient‐reported and economic outcomes in US patients with type 2 diabetes using basal insulin

Aims

To evaluate the clinical and patient‐reported outcomes and healthcare utilization and costs associated with patient‐reported hypoglycaemia in US adults with type 2 diabetes (T2D) treated with basal insulin.

Materials and methods

This was an observational, cross‐sectional, survey‐based study of adults with T2D on basal insulin ± oral antidiabetes drugs (OADs) or rapid‐acting/premixed insulin, who had in the past ever experienced hypoglycaemia, using US data from the National Health and Wellness Survey. Eligible patients were categorized as having no hypoglycaemia (38.7%), non‐severe hypoglycaemia (55.1%), or severe hypoglycaemia (6.2%) in the preceding 3 months. Outcomes included health‐related quality of life (HRQoL), work productivity and activity impairment, healthcare resource utilization, and estimated direct and indirect costs. Multivariable regression models were performed to control for patient characteristics.

Results

Patients who experienced severe hypoglycaemia had significantly (P < .05) lower HRQoL scores, greater overall impairment of work productivity and activity, greater healthcare resource utilization, and higher costs compared with those who experienced non‐severe or no hypoglycaemia. Patients with non‐severe hypoglycaemia also reported an impact on the number of provider visits, indirect costs, and HRQoL.

Conclusions

Patients with T2D using basal insulin ± OADs or rapid‐acting/premixed insulin in the United States who experienced severe hypoglycaemia had greater impairment of activity and work productivity, utilized more healthcare resources, and incurred higher associated costs than those with non‐severe or no hypoglycaemia. The study also demonstrated the impact that non‐severe hypoglycaemic events have on economic and HRQoL outcomes. Reducing the incidence and severity of hypoglycaemia could lead to clinically meaningful improvements in HRQoL and may result in lower healthcare utilization and associated costs.     

Serious, prolonged hypoglycaemia with glibenclamide in a patient with Mendenhall's syndrome

Mendenhall's syndrome, characterized by familial insulin resistant diabetes, pineal hyperplasia and multiple somatic abnormalities, is associated with defects involving the a-subunit of the insulin receptor. The associated insulin-resistant diabetes is extremely difficult to treat; insulin is required in very large doses to control hyperglycaemia and oral hypoglycaemic agents are ineffective. We report a case of severe, prolonged hypoglycaemia that occurred in a 24-year-old patient with Mendenhall's syndrome following therapy with glibenclamide. He had glibenclamide 10 mg daily for 1 week following which he was admitted to hospital in hypoglycaemic coma with blood glucose levels < 1 0 mmol/l. This subject had undergone hypophysectomy at the age of 11 years. Prior to pituitary ablation, oral hypoglycaemic agents did not improve glycaemic control. Thus, previous hypophysectomy in this patient appears to have made it possible for glibenclamide to exert its hypoglycaemic effect. The occurrence of hypoglycaemia in this patient suggests alternative mechanisms for insulin action in conditions characterized by severe insulin resistance due to insulin receptor defects.     

Antecedent hypoglycaemia attenuates vascular endothelial growth factor response to subsequent hypoglycaemia in healthy men

Aim The plasma concentration of vascular endothelial growth factor (VEGF) has recently been shown to increase sharply in response to hypoglycaemia and, thus, has been proposed as having a role in hypoglycaemia counter‐regulation. Many counter‐regulatory hormones show a reduced response after antecedent hypoglycaemia. We therefore investigated whether this decrease in responsiveness with repetitive hypoglycaemia also pertains to VEGF. Methods Three hypoglycaemic clamp experiments were performed on two consecutive days in 15 healthy men. VEGF response was assessed during the first and last hypoglycaemic period. Results As expected, plasma VEGF concentrations rose markedly during the clamps (P < 0.001). The increase was distinctly blunted during the third (+13 ± 8 pg/ml) as compared with the first (+54 ± 18 pg/ml) hypoglycaemic clamp (P = 0.046). Conclusion This data confirms that circulating VEGF concentrations increase acutely during hypoglycaemia. Like the counter‐regulatory hormones, the hypoglycaemia‐induced rise in VEGF is attenuated after antecedent hypoglycaemia. The origin of increased systemic VEGF concentration during hypoglycaemia and its physiological role remains to be defined.     

Hypoglycaemia in insulin-treated Type 2 diabetes: frequency,symptoms and impaired awareness

Aims Hypoglycaemia is considered to be less common in people with insulin-treated Type 2 diabetes than in Type 1 diabetes. A retrospective survey was made of 215 people with insulin-treated Type 2 diabetes to quantify the frequency and nature of hypoglycaemia experienced. Methods The frequencies of mild (self-treated) and severe (required assistance) hypoglycaemia during the preceding year were estimated retrospectively. The usual symptoms of hypoglycaemia and state of awareness of hypoglycaemia were scored using validated questionnaires and any history suggestive of impaired hypoglycaemia awareness was documented. Results In this cohort, 157 (73%) had experienced hypoglycaemia since commencing insulin, the frequency of which increased with duration of diabetes and of insulin therapy and was inversely related to current HbA_1c (all P < 0.05). During the preceding year, 32 individuals (15%) had experienced severe hypoglycaemia, with an estimated incidence for the entire group of 0.28 episodes/patient/year. Principal components analysis revealed two underlying symptom groups (autonomic and neuroglycopenic), similar to those reported previously by young adults with Type 1 diabetes, but the total symptom score declined with advancing age. Of the 157 with a history of hypoglycaemia, the 13 (8%) individuals who gave a history of impaired awareness of hypoglycaemia had experienced a ninefold higher incidence of severe hypoglycaemia than those with normal awareness, and reported experiencing mainly neuroglycopenic symptoms. Conclusions While the overall frequencies of mild and severe hypoglycaemia were lower in insulin-treated Type 2 diabetes than have been reported previously in Type 1 diabetes, the risk of hypoglycaemia was greater with increasing duration of diabetes and of insulin therapy. Although impaired awareness of hypoglycaemia was uncommon, it was associated with a higher incidence of severe hypoglycaemia. Diabet. Med. 20, ***–*** (2003)     

Reversible amnesia in a Type 1 diabetic patient and bilateral hippocampal lesions on magnetic resonance imaging (MRI).

AIMS: Intensive insulin therapy of Type 1 diabetes limits its chronic complications, but is associated with an increased risk of severe hypoglycaemia and its neuroglycopenic consequences. METHODS: Case report. RESULTS: A 24-year-old male with 15 years' history of Type 1 diabetes, who was missing for 48 h, was found at home in ketoacidosis coma. Intensive care permitted a rapid improvement revealing an unexpected severe anterograde amnesia, confirmed by neuropsychological testing. MRI performed 4 days after admission showed abnormal bilateral hyperintensity signals on T2-weighted images in the hippocampus. Three months later, the patient had nearly completely recovered and resumed work. MR images and neuropsychological testing returned to normal. CONCLUSIONS: The most likely course of events favours an initial prolonged hypoglycaemic coma following insulin overdose. The hippocampal injury may be a result of hypoglycaemia. Neuropsychological testing and MRI abnormalities were completely reversible. This case underlines the potential risks of intensive insulin therapy.     

Reversible cognitive deterioration after a single episode of severe hypoglycaemia: a case report.

A case of a male 34-year-old Type 1 diabetic patient who experienced a prolonged severe hypoglycaemic episode is presented. After the hypoglycaemic event, the patient suffered from moderate to severe neuropsychological impairments. On the basis of neuropsychological assessment results, diabetes therapy was modified (less complex insulin regimen, fixed insulin doses and fixed carbohydrate distribution). At a follow-up examination (3 months), presumable complete recovery of cognitive function was observed. This case demonstrates the possible detrimental neuropsychological effects of severe hypoglycaemia, that, in this case, turned out to be reversible. It highlights the clinical implications of impaired cognitive function on self-care and self-management abilities and the usefulness of neuropsychological testing in clinical diabetes care.     

A retrospective observational study of people with Type 1 diabetes with self‐reported severe hypoglycaemia reveals high level of ambulance attendance but low levels of therapy change and specialist intervention

Aim

To evaluate the impact of severe hypoglycaemia on NHS resources and overall glycaemic control in adults with Type 1 diabetes.

Methods

An observational, retrospective study of adults (aged ≥ 18 years) with Type 1 diabetes reporting one or more episodes of severe hypoglycaemia during the preceding 24 months in 10 NHS hospital diabetes centres in England and Wales. The primary outcome was healthcare resource utilization associated with severe hypoglycaemia. Secondary outcomes included demographic and clinical characteristics, diabetes control and pathway of care.

Results

Some 140 episodes of severe hypoglycaemia were reported by 85 people during the 2‐year observation period. Ambulances were called in 99 of 140 (71%) episodes and Accident and Emergency attendance occurred in 26 of 140 (19%) episodes, whereas 29 of 140 (21%) episode required no immediate help from healthcare providers. Participants attended a median of 5 (range 0–58) diabetes clinic consultations during the observation period; 13% (70 of 552) of all consultations were severe hypoglycaemia‐related. Of the HbA_1c measurements recorded closest prior to severe hypoglycaemia (n = 119), only 7 of 119 measurements were < 48 mmol/mol (< 6.5%) and mean HbA_1c was 70 (sd 19) mmol/mol (8.5%, sd 1.7%). Some 119 changes to diabetes treatment were recorded during the observation period (median/person 0;, range 0–11), of which 52 of 119 changes (44%) followed severe hypoglycaemic events.

Conclusions

We observed a high level of ambulance service intervention but surprisingly low levels of hypoglycaemia follow‐up, therapy change and specialist intervention in people self‐reporting severe hypoglycaemia. These results suggest there may be important gaps in care pathways for people with Type 1 diabetes self‐reporting severe hypoglycaemia.     

Case report of chloroquine therapy and hypoglycaemia in type 1 diabetes: What should we have in mind during the COVID-19 pandemic?

A type 1 diabetes patient experienced remission associated with chloroquine therapy while travelling to a malaria-endemic area. Chloroquine has immunomodulatory and hypoglycaemic effects and may become more frequently used due to the COVID-19 pandemic. Patients with type 1 diabetes treated with chloroquine should be monitored for hypoglycaemia, even after recovery.     

Non-insulinoma persistent hyperinsulinaemic hypoglycaemia caused by an activating glucokinase mutation: hypoglycaemia unawareness and attacks

Objective Adult‐onset non‐insulinoma persistent hyperinsulinaemic hypoglycaemia (NI‐PHH) and the variant NI‐pancreatogenous hypoglycaemia syndrome (NIPHS) are genetically unexplained diseases, without reports of hypoglycaemia unawareness or familial inheritance. Design and patients In a prospective 8‐year follow‐up, a boy (i) with NI‐PHH since age 14 years, his mother (ii), the mother's brother (iii) and his daughter (iv) were studied. Results Patient (i) was characterized by especially postprandial hypoglycaemia down to 1·6 mmol/l and pronounced variability in diazoxide need with obesity; (ii) had asymptomatic blood glucose down to 2·9 mmol/l, but a severe hypoglycaemic postprandial attack after a slimming diet; (iii) had moderate hypoglycaemic symptoms since childhood and need of frequent eating; and (iv) was asymptomatic until a hypoglycaemic accident in the age of 24. After a slimming diet, symptomatic fasting, but especially postprandial hypoglycaemia occurred (blood glucose 1·9 mmol/l after 19 h fasting; 1·6 mmol/l 3·5 h after OGTT). By CT‐scan/endoscopic ultrasound in three of the individuals, insulinoma could not be detected. In all four individuals, an activating glucokinase (GCK) mutation A456V was found. No mutations were found in the ABCC8 or KCNJ11 genes. The patients responded to treatment with diazoxide or octreotide long acting release. Conclusion This is the first report to highlight a genetic cause to adult‐onset NI‐PHH/NIPHS. The activating GCK mutation was dominantly inherited, but only after year‐long follow‐up and investigations, other family members were diagnosed symptomatic. Hypoglycaemia unawareness seems to be a prominent feature, but hypoglycaemic attacks occur after slimming, especially postprandially. PHH‐GCK was medical responsive.     

Changing the glucose cut-off values that define hypoglycaemia has a major effect on reported frequencies of hypoglycaemia

Aims/hypothesis  The aim of this analysis was to quantify the relationship between the frequency of hypoglycaemia and various glucose cut-off points for the definition of hypoglycaemia, within a range of HbA_1c strata. Methods  Data from two trials examining insulin glargine dose titration in 12,837 type 2 diabetic participants starting insulin therapy were combined. Curves for hypoglycaemia frequency plotted against endpoint HbA_1c level were constructed, using a range of glucose cut-off points for hypoglycaemia. Results  During the 12-week study period, 3,912 patients recorded 21,592 hypoglycaemic episodes, comprising 242 severe, 8,871 symptomatic and 12,479 asymptomatic events, corresponding to hypoglycaemia event rates of 0.10, 3.8 and 5.3 events per patient year. Increasing the hypoglycaemia cut-off point from, for instance, <3.1 to <3.9 mmol/l more than doubled the percentage of affected patients, e.g. from 17.7 to 43.3% at HbA_1c 7.0–7.2%. At higher hypoglycaemia cut-off points the proportion of patients having only asymptomatic hypoglycaemia increased, e.g. from 30.7% at <3.1 mmol/l to 61.7% of patients at a cut-off point of <3.9 mmol/l. In sensitivity analysis, 121 of 1,756 patients with at least one self-monitored blood glucose value <3.1 mmol/l experienced severe hypoglycaemia, compared with 149 of 3,912 patients with a self-monitored blood glucose level of <3.9 mmol/l. Thus, to identify 28 more patients with severe hypoglycaemia, the number of patients experiencing only non-severe hypoglycaemia more than doubled. Conclusions/interpretation  The glucose cut-off point defining hypoglycaemia greatly affects the reported frequency of hypoglycaemia. When hypoglycaemia is to be defined by a predetermined glucose level, to have clinical relevance the cut-off should be set at a lower level than the threshold of 3.9 mmol/l proposed by the American Diabetes Association. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Prospective assessment of severe hypoglycaemia in diabetic children and adolescents with impaired and normal awareness of hypoglycaemia

Summary To establish whether impaired hypoglycaemic awareness is associated with increased rate of severe hypoglycaemia and to assess clinical predictors of severe episodes without warning symptoms a prospective study of 130 insulin-dependent diabetic children and adolescents was undertaken for 1 year. Using a structured questionnaire, 48 patients reported impaired awareness and 82 reported normal awareness of hypoglycaemia at baseline of the study. The two groups did not differ regarding clinical and metabolic characteristics. Episodes of severe hypoglycaemia were recorded for 1 year. The rate of severe hypoglycaemia was higher in the group with impaired awareness than in the group with normal awareness (p < 0.0001). Of the severe hypoglycaemic episodes, 34.0 % developed without warning symptoms. Patients with impaired awareness experienced more severe episodes without warning symptoms than those with normal awareness (p = 0.0054). Severe hypoglycaemia occurred more frequently in patients with impaired awareness aged 6 years and less (p = 0.0041) than in older counterparts. Impaired awareness reported at baseline [adjusted odds ratio (OR): 5.8; p = 0.0021], age 6 years or less (3.4; p = 0.0121), previous severe episode (4.8; p = 0.0043) and more than 5 % of home blood glucose readings 3.3 mmol/l or less in the preceding month (4.2; p = 0.0211) proved to be independently predictive of severe hypoglycaemic events without warning symptoms. In conclusion, impaired hypoglycaemic awareness is associated with an increased rate of severe hypoglycaemia in diabetic children and adolescents. One third of severe episodes developed without warning symptoms. Impaired awareness, young age and recent biochemical or severe hypoglycaemias are independent risk factors for such episodes. Avoidance of hypoglycaemia should be a priority in pre-school children with diabetes. [Diabetologia (1998) 41: 898–903] Received: 15 December 1997 and in revised form: 5 March 1998     

Cumulative cognitive impairment following recurrent severe hypoglycaemia in adult patients with insulin-treated diabetes mellitus

Summary To examine the hypothesis that episodes of severe hypoglycaemia may cause cumulative cognitive impairment, 100 Type 1 (insulin-dependent) diabetic patients were examined. Their age range was 25–52 years, and the onset of diabetes had occurred after the age of 19 years. Patients with evidence of organic brain disease, including cerebrovascular disease, were excluded. A questionnaire was used to assess the number, frequency and severity of hypoglycaemic episodes experienced during treatment with insulin and the accuracy of this retrospective information was verified from general practice and hospital case-notes. A detailed neuropsychological assessment was undertaken, including tests of pre-morbid and present IQ (Wechsler-Revised), memory and information-processing speed. Significant correlations were observed between the frequency of severe hypoglycaemia and the magnitude of intellectual decline, Performance IQ, inspection time and reaction time (patients with the more frequent hypoglycaemia had poorer performance). Two sub-groups of patients were identified on the basis of their experience of severe hypoglycaemia, and were balanced for pre-morbid IQ, age and duration of diabetes. One sub-group (n=23) had never experienced severe hypoglycaemia (Group A), whilst the other sub-group (n=24) had suffered at least five episodes of severe hypoglycaemia (Group B). Group B had greater intellectual impairment than Group A, and Group B also had a significantly slower mean reaction time and higher reaction time variance when compared with Group A. It is concluded that recurrent severe hypoglycaemia is associated with cumulative cognitive impairment in adult diabetic patients treated with insulin.     

Symptomatic hypoglycaemia in 411 type 1 diabetic patients

The frequency of symptomatic hypoglycaemic episodes was studied in 411 randomly selected conventionally treated Type 1 diabetic out-patients. Between two consecutive visits to the out-patient clinic each patient filled in a questionnaire at home. The number of hypoglycaemic episodes was then recorded prospectively in a diary for 1 week. From the questionnaires, the (retrospective) frequencies of mild and severe symptomatic hypoglycaemia were 1.6 and 0.029 episodes patient-1 week-1. From the diaries, the (prospective) frequencies of mild and severe hypoglycaemic episodes were 1.8 and 0.027 patient-1 week-1. Symptomatic hypoglycaemia was more frequent on working days than during weekends (1.8:1) and more frequent in the morning than during the afternoon, evening, and night (4.5:2.2:1.4:1). The symptoms of hypoglycaemia were non-specific, heterogeneous, and weakened with increasing duration of diabetes. During their diabetic life, 36% of the patients had experienced hypoglycaemic coma. The frequency of hypoglycaemia was positively, but only weakly, correlated with insulin dose, number of injections, percentage unmodified insulin of the total dose, and HbA1c (mild hypoglycaemia only). The frequency was also negatively, but weakly, correlated with age and HbA1c (episodes with coma only), but not correlated with sex, duration of diabetes, or patients' ratings of worries about mild and severe hypoglycaemia.     

Hypoglycaemia in Type 2 diabetes

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self‐reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications.     

Extensive central and extrapontine myelinolysis in a case of chronic alcoholism without hyponatremia: a case report with analysis of serial MR findings

We observed a 41-year-old woman with severe central pontine myelinolysis (CPM) and unusually extensive extrapontine myelinolysis (EPM), but without evidence of hyponatremia. Increased alcohol consumption in prior months was the main cause of her CPM/EPM. However, in general, EPM is a rare accompaniment in alcoholic patients with CPM without hyponatremia. With regard to our patient, the EPM was unusually widespread; magnetic resonance imaging (MRI) of her brain showed multiple hyperintense lesions on T2-weighted images distributed symmetrically in bilateral caudate nuclei, lentiform nuclei and thalami. Serial follow-up MRI revealed almost complete resolution of EPM after methylprednisolone pulse therapy. By contrast, marked cavitary hypointensity in the pons remained, but complete remission of neurological symptoms was achieved.