Gregory C. Jones

Trends in recorded capillary blood glucose and hypoglycaemia in hospitalised patients with diabetes

AIMS To utilise whole-system analysis of capillary glucose measurement results to examine trends in timing of glucose monitoring, and to investigate whether these timings are appropriate based on observed patterns of hypoglycaemia. METHODS Near-patient capillary blood glucose results from eight acute hospitals collected over 57 months were analysed. Analysis of frequency of measurement, and measurements in the hypoglycaemic (<4mmol/l) and severe hypoglycaemic (<2.5mol/l) range per time of day was made. RESULTS 3345241 capillary glucose measurements were analysed. 1657594 capillary blood glucose values were associated with 106624 admissions in those categorised as having diabetes. Large peaks in frequency of glucose measurements occurred before meals, with the highest frequency of capillary glucose measurement activity being seen pre-breakfast. Overnight, an increase in measurement activity was seen each hour. This pattern was mirrored by frequency of measured hypoglycaemia. 27968 admissions (26.2%) were associated with at least one hypoglycaemic measurement. A greater proportion of measurements were within the hypoglycaemic range overnight with 61.7% of all hypoglycaemia between 2100 and 0900h, with peak risk of measured capillary glucose being hypoglycaemic between 0300 and 0400h. CONCLUSIONS Hypoglycaemic is common with the greatest risk of hypoglycaemia overnight and a peak percentage of all readings taken being in the hypoglycaemic range between 0300 and 0400h. Measurement activity overnight was driven by routine, with patterns of proportion of measurements in the hypoglycaemic range indicating that there may be a significant burden of undiscovered hypoglycaemia in the patients not routinely checked overnight.

Inpatient Glycemic Variability and Long-Term Mortality in Hospitalized Patients with Type 2 Diabetes

AIMS/HYPOTHESIS To determine the association between inpatient glycemic variability and long-term mortality in patients with type 2 diabetes mellitus. METHODS Capillary blood glucose (CBG) of inpatients from 8 hospitals was analysed. 28,353 admissions identified were matched for age, duration of diabetes and admission and median and interquartile range of CBG. 6year mortality was investigated for (i) those with CBG IQR in the top half of all IQR measurements (matched for all except IQR), vs those in the lower half and (ii) those with the lowest quartile median glucose (matched for all except median). RESULTS CONCLUSION: Higher inpatient glycemic variability is associated with increased mortality on long-term follow up. When matched by IQR, we have demonstrated higher median CBG is associated with lower long-term mortality. CBG variability may increase cardiovascular morbidity by increasing exposure to hypoglycaemia or to variability per se. In hospitalized patients with diabetes, glycemic variability should be minimised and when greater CBG variability is unavoidable, a less stringent CBG target considered.

Comment on ‘A justification for less restrictive guidelines on the use of metformin in stable chronic renal failure’

We read with interest the article by Adam and O’Brien [1] on the use of metformin in stable chronic renal failure. Whilst we agree that lactic acidosis is a very rare complication that should not restrict metformin usage unnecessarily, we feel that using lower doses of metformin to achieve predicted plasma metformin levels of < 10 mg/l cannot be justified. In patients with estimated glomerular filtration rates of 10–19 ml/min a dose of 500 mg is recommended. Whilst it may be safe to use this dose of metformin, it is unlikely to be effective in lowering glucose. There is no evidence that efficacy of metformin is related to plasma levels of the drug. Intravenous metformin has no effect on fasting glucose, C-peptide or insulin levels, hepatic glucose production or peripheral glucose disposal [2,3]. Recent evidence suggests that metformin action is modulated by lower gut delivery and therefore dose delivery to this area and not plasma concentration predicts hypoglycaemic efficacy [4]. This would of course mean that in patients with renal insufficiency, despite metformin plasma levels being equivalent with lower dosing, that efficacy would be impaired or absent. We therefore do not think that the use of low-dose metformin in renal failure is justified.

A Practical Approach to Glucose Abnormalities in Cystic Fibrosis

Cystic fibrosis is a common genetic condition and abnormal glucose handling leading to cystic fibrosis-related diabetes (CFRD) is a frequent comorbidity. CFRD is mainly thought to be the result of progressive pancreatic damage resulting in beta cell dysfunction and loss of insulin secretion. Whilst Oral Glucose Tolerance Testing is still recommended for diagnosing CFRD, the relationship between glucose abnormalities and adverse outcomes in CF is complex and occurs at stages of dysglycaemia occurring prior to diagnosis of diabetes by World Health Organisation criteria. Insulin remains the mainstay of treatment of CF-related glucose abnormalities but the timing of insulin commencement, optimum insulin regime and targets of glycaemic control are not clear. These complexities are compounded by common issues with nutritional status, need for enteral feeding, steroid use and high disease burden on CF patients.

HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes

Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups.

Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long-term HbA1c and HbA1c variability

Previous evidence has demonstrated that participation in the Dose Adjustment for Normal Eating (DAFNE) education programme can reduce HbA1c and severe hypoglycaemia in people with Type 1 diabetes. In a number of studies, increased HbA1c variability has been associated with higher diabetic morbidity and mortality. No studies have examined the impact of structured education on HbA1c variability in Type 1 diabetes.

Visit-to-visit HbA1c variability and systolic blood pressure (SBP) variability are significantly and additively associated with mortality in individuals with type 1 diabetes: An observational study

To investigate the relationship between variability in both visit‐to‐visit HbA1c and SBP and mortality in individuals with type 1 diabetes.

Hypoglycemia and Clinical Outcomes in Hospitalized Patients With Diabetes: Does Association With Adverse Outcomes Remain When Number of Glucose Tests Performed Is Accounted For?

Background: Hypoglycemia is associated with increased length of stay in hospital patients, but previous studies have not considered the confounding effect of increased hypoglycemia detection associated with increased capillary blood glucose (CBG) measurement in prolonged admissions. We aimed to determine the effect of recorded hypoglycemia on length of stay of hospital inpatients (LOS) when this mathematical association is subtracted. Methods: CBG data were analyzed for inpatients within our health board area (01/2009-01/2015). A simulated CBG data set was generated for each patient with an identical sampling frequency to the measured CBG data set. The mathematical component of increased LOS was determined using the simulated data set. Subtraction of this confounding mathematical association was used to provide measurement of the true clinical association between recorded hypoglycemia (CBG < 4 mmol [< 72mg/dl]) and LOS. Results: A total of 196 962 admissions of 52 475 individuals with known diabetes were analyzed. 68 809 admissions of 29 551 individuals had >4 CBG measurements made and were included in analysis. After subtraction of the mathematical association of increased sample number, the clinical effect of recorded hypoglycemia is reduced—but persists—compared to previous studies. 1-2 days with recorded hypoglycemia has a relatively minor effect on LOS. LOS increases rapidly if there are ≥3 days with recorded hypoglycemia, with an increase of 0.75 days LOS per additional day with hypoglycemia. Conclusions: This technique increases accuracy of economic modeling of the impact of hypoglycemia on health care systems. This could assist study of the impact of hypoglycemia on other outcomes by factoring for bias of increased sample numbers.

Co-enzyme Q10

reduced systolic blood pressure(BP) by a range of 11–17mmHg anddiastolic BP by a range of 8–10mmHgin hypertensive patients. There are several limitations to the result of thismeta-analysis. Nine of the studiesstopped their subjects’ antihyperten-sives two weeks prior to the study. Thisresulted in a high pre-study BP, hencethe range of BP reduction may be far lower in a clinical setting wherepatients are established on traditionalantihypertensives. The dose of CoQ

Boerhaave's syndrome and diabetic ketoacidosis

Boerhaave described spontaneous rupture of the oesophagus in 1724. This is a transmural perforation, most typically caused by forceful vomiting. It is important to distinguish from a Mallory-Weiss tear, which is a non-transmural perforation. The perforation almost invariably occurs at the same anatomical site. A weakness in the distal oesophageal wall is suspected, but this has not been confirmed by anatomical studies.1 Oesophageal rupture is thought to arise from a sudden rise in intraluminal oesophageal pressure produced during vomiting, and failure of the cricopharyngeal muscles to relax.2 Boerhaave’s syndrome is most commonly caused by repeated vomiting and retching. This is frequently caused by excess food and/or alcohol. The classic triad of symptoms is vomiting, lower thoracic pain, and surgical emphysema. However, symptoms and signs will depend on the location of the tear, the cause of the tear, and the length of time from rupture to diagnosis and treatment. Diagnosis can be difficult, as often there are no classic symptoms, and delays in presentation for medical care are common.