Suzy Hope

Urine C-peptide creatinine ratio is an alternative to stimulated serum C-peptide measurement in late-onset, insulin-treated diabetes.

Diabet. Med. 28, 1034–1038 (2011)

CAGE, RAPS4, RAPS4-QF and AUDIT Screening Tests for Men and Women Admitted for Acute Alcohol Intoxication to an Emergency Department: Are Standard Thresholds Appropriate?

AIMS A number of screening instruments are routinely used in Emergency Department (ED) situations to identify alcohol-use disorders (AUD). We wished to study the psychometric features, particularly concerning optimal thresholds scores (TSs), of four assessment scales frequently used to screen for abuse and/or dependence, the cut-down annoyed guilty eye-opener (CAGE), Rapid Alcohol Problem Screen 4 (RAPS4), RAPS4-quantity-frequency and AUD Identification Test (AUDIT) questionnaires, particularly in the sub-group of people admitted for acute alcohol intoxication (AAI). METHODS All included patients [AAI admitted to ED (blood alcohol level ≥0.8 g/l)] were assessed by the four scales, and with a gold standard (alcohol dependence/abuse section of the Mini International Neuropsychiatric Interview), to determine AUD status. To investigate the TSs of the scales, we used Youdens index, efficiency, receiver operating characteristic (ROC) curve techniques and quality ROC curve technique for optimized TS (indices of quality). RESULTS A total of 164 persons (122 males, 42 females) were included in the study. Nineteen (11.60%) were identified as alcohol abusers alone and 128 (78.1%) as alcohol dependents (DSM-IV). Results suggest a statistically significant difference between men and women (P < 0.05) in performance of the screening tests RAPS4 (≥1) and CAGE (≥2) for detecting abuse. Also, in this population, we show an increase in TSs of RAPS4 (≥2) and CAGE (≥3) for detecting dependence compared with those typically accepted in non-intoxicated individuals. The AUDIT test demonstrates good performance for detecting alcohol abuse and/or alcohol-dependent patients (≥7 for women and ≥12 for men) and for distinguishing alcohol dependence (≥11 for women and ≥14 for men) from other conditions. CONCLUSION Our study underscores for the first time the need to adapt, taking into account gender, the thresholds of tests typically used for detection of abuse and dependence in this population.

Practical Classification Guidelines for Diabetes in patients treated with insulin: a cross-sectional study of the accuracy of diabetes diagnosis.

Background Differentiating between type 1 and type 2 diabetes is fundamental to ensuring appropriate management of patients, but can be challenging, especially when treating with insulin. The 2010 UK Practical Classification Guidelines for Diabetes were developed to help make the differentiation. Aim To assess diagnostic accuracy of the UK guidelines against ‘gold standard’ definitions of type 1 and type 2 diabetes based on measured C-peptide levels. Design and setting In total, 601 adults with insulin-treated diabetes and diabetes duration ≥5 years were recruited in Devon, Northamptonshire, and Leicestershire. Method Baseline information and home urine sample were collected. Urinary C-peptide creatinine ratio (UCPCR) measures endogenous insulin production. Gold standard type 1 diabetes was defined as continuous insulin treatment within 3 years of diagnosis and absolute insulin deficiency (UCPCR<0.2 nmol/mmol ≥5 years post-diagnosis); all others classed as having type 2 diabetes. Diagnostic performance of the clinical criteria was assessed and other criteria explored using receiver operating characteristic (ROC) curves. Results UK guidelines correctly classified 86% of participants. Most misclassifications occurred in patients classed as having type 1 diabetes who had significant endogenous insulin levels (57 out of 601; 9%); most in those diagnosed ≥35 years and treated with insulin from diagnosis, where 37 out of 66 (56%) were misclassified. Time to insulin and age at diagnosis performed best in predicting long-term endogenous insulin production (ROC AUC = 0.904 and 0.871); BMI was a less strong predictor of diabetes type (AUC = 0.824). Conclusion Current UK guidelines provide a pragmatic clinical approach to classification reflecting long-term endogenous insulin production; caution is needed in older patients commencing insulin from diagnosis, where misclassification rates are increased.

Random non-fasting C-peptide: bringing robust assessment of endogenous insulin secretion to the clinic.

Measuring endogenous insulin secretion using C–peptide can assist diabetes management, but standard stimulation tests are impractical for clinical use. Random non‐fasting C–peptide assessment would allow testing when a patient is seen in clinic.

Assessment of endogenous insulin secretion in insulin treated diabetes predicts postprandial glucose and treatment response to prandial insulin

BackgroundIn patients with both Type 1 and Type 2 diabetes endogenous insulin secretion falls with time which changes treatment requirements, however direct measurement of endogenous insulin secretion is rarely performed. We aimed to assess the impact of endogenous insulin secretion on postprandial glucose increase and the effectiveness of prandial exogenous insulin.MethodsWe assessed endogenous insulin secretion in 102 participants with insulin treated diabetes (58 Type 1) following a standardised mixed meal without exogenous insulin. We tested the relationship between endogenous insulin secretion and post meal hyperglycaemia. In 80 participants treated with fast acting breakfast insulin we repeated the mixed meal with participants’ usual insulin given and assessed the impact of endogenous insulin secretion on response to exogenous prandial insulin.ResultsPost meal glucose increment (90 minute - fasting) was inversely correlated with endogenous insulin secretion (90 minute C-peptide) (Spearman’s r = −0.70, p < 0.001). Similar doses of exogenous prandial insulin lowered glucose increment more when patients had less endogenous insulin; by 6.4(4.2-11.1) verses 1.2(0.03-2.88) mmol/L (p < 0.001) for patients in the lowest verses highest tertiles of endogenous insulin.ConclusionsIn insulin treated patients the measurement of endogenous insulin secretion may help predict the degree of postprandial hyperglycaemia and the likely response to prandial insulin.

Urinary C-peptide creatinine ratio detects absolute insulin deficiency in Type 2 diabetes.

To determine the prevalence and clinical characteristics of absolute insulin deficiency in long‐standing Type 2 diabetes, using a strategy based on home urinary C‐peptide creatinine ratio measurement.

Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative.

Rates of population ageing are unprecedented and this, combined with the progressive urbanization of lifestyles, has led to a dramatic shift in the epidemiology of diabetes towards old age, particularly to those aged 60–79 years. Both ageing and diabetes are recognized as important risk factors for the development of functional decline and disability. In addition, diabetes is associated with a high economic, social and health burden. Traditional macrovascular and microvascular complications of diabetes appear to account for less than half of the diabetes‐related disability observed in older people. Despite this, older adults are under‐represented in clinical trials. Guidelines from organizations such as the National Institute for Health and Care Excellence (NICE), the European Association for the Study of Diabetes, and the American Diabetes Association acknowledge the need for individualized care, but the glycaemic targets that are suggested to constitute good control [HbA1c 53–59 mmol/mol (7–7.5%)] are too tight for frail older individuals. We present a framework for the assessment of older adults and guidelines for the management of this population according to their frailty status, with the intention of reducing complications and improving quality of life for these people.

Intravascular lymphoma presenting with postural hypotension

An 84-year-old woman presented with severe postural hypotension. Further assessment revealed weight loss, fatigue and fever at night. On examination, she had bilateral skin lesions on the inner thighs and skin biopsy revealed intravascular high grade B cell lymphoma. This was successfully treated with curative chemotherapy. The cause of the postural hypotension in this case was felt likely to be autonomic neuropathy caused by neurovascular infiltration by intravascular lymphoma. Treatment of the lymphoma has resolved the postural hypotension, although some symptoms of postural instability persist.

Are we missing hypoglycaemia? Elderly patients with insulin-treated diabetes present to primary care frequently with non-specific symptoms associated with hypoglycaemia

Highlights • Non-specific symptoms make hypoglycaemia recognition difficult in older patients• Patients aged >65 commonly present to primary care with non-specific symptoms• Those with documented hypos present more on other occasions with non-specific symptoms, which could represent unrecognised hypoglycaemia• Nausea, falls & unsteadiness were more common in these patients.

Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes

Abstract Background National Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT). Methods 191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT. Findings 11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m 2 vs 29, p=0·04) but no other significant differences in clinical characteristics. Interpretation We have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin. Funding National Institute for Health Research.