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

BackgroundNational 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).Methods191 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.Findings11 (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 <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m² vs 29, p=0·04) but no other significant differences in clinical characteristics.InterpretationWe 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.FundingNational Institute for Health Research.     

Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

Specific immunotherapy for severe latex allergy

We studied 4 patients (3 adult females + 13y old boy) with latex allergy. All patients had anaphylaxis related with latex and oral-latex-fruit syndrome. All 3 females had severe symptoms in the workplace. The boy had spina bifida with 9 previous surgeries and needed further surgical interventions. Positive skin prick tests (SPT), the presence of serum latex specific IgE (CAP-RAST, Pharmacia-Upjohn, Sweden- class 3 in the 3 females and class 4 in the boy) demonstrated the sensitisation. All 4 patients were treated with specific immunotherapy (SIT) with aqueous extract (ALK-ALK-ABELLO SA, Spain) administered subcutaneously at the hospital, by a modified rush schedule. A maintenance dose (MD) of 0.35_g protein was established according to the magnitude of local reactions (LRs). In one patient a higher dose induced the appearance of a systemic reaction (SR) 40 min after administration, which promptly remitted with treatment. After reaching MD, all 3 females remained assymptomatic at workplace. A challenge test with latex gloves was performed. Two months after MD was reached 2 females had no symptoms and one other had mild symptoms of rhinoconjunctivitis. The boy was subjected to a surgical intervention with no allergic reaction. We also observed a reduction on skin reactivity to latex in all patients by prick tests. We consider SIT with latex to be highly effective, safe and well tolerated provided we use this dose of the allergenic extract.     

Right heart pressure determination by Doppler in infants with tricuspid regurgitation

Doppler and direct measurements of right ventricle to right atrial pressure drop were made during cardiac catheterisation on 28 occasions in 26 infants with congenital heart disease. Age was 10 days to 12 months (median 4.5 months), and weight was 3.1 to 9.0 kg (median 4.7 kg). We measured peak velocity of tricuspid regurgitation by continuous wave Doppler, and the pressure drop was calculated using the modified Bernoulli equation (delta p = 4v2). There was a high correlation (r = 0.95) between direct and Doppler measurements. Doppler values tended to underestimate the right ventricle to right atrial pressure drop, but this was not of clinical significance (mean 2 mm Hg). The 95% confidence interval for the Doppler velocity was -0.41 to +0.26 m/sec, and was consistent across the range of pressures studied. Variability between observers was tested, by two observers performing sequential paired examinations on 16 newborn babies with tricuspid regurgitation. The coefficient of repeatability was 6.3 mm Hg (95% confidence interval 4.7 to 9.5 mm Hg) or 0.26 m/sec (0.18 to 0.50 m/sec). This method of right ventricular pressure estimation, validated previously only in older children and adults, is a reproducible and accurate technique in infants with tricuspid regurgitation.     

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.