Proinsulin is stable at room temperature for 24 hours in EDTA:A clinical laboratory analysis (adAPT 3)

AIMS:Reference laboratories advise immediate separation and freezing of samples for the assay of proinsulin, which limit its practicability for smaller centres. Following the demonstration that insulin and C-peptide are stable in EDTA at room temperature for at least 24hours, we undertook simple stability studies to establish whether the same might apply to proinsulin. METHODS:Venous blood samples were drawn from six adult women, some fasting, some not, aliquoted and assayed immediately and after storage at either 4°C or ambient temperature for periods from 2h to 24h. RESULTS:There was no significant variation or difference with storage time or storage condition in either individual or group analysis. CONCLUSION:Proinsulin appears to be stable at room temperature in EDTA for at least 24h. Immediate separation and storage on ice of samples for proinsulin assay is not necessary, which will simplify sample transport, particularly for multicentre trials

Is a Priming Dose of Insulin Necessary in a Low-Dose Insulin Protocol for the Treatment of Diabetic Ketoacidosis?

OBJECTIVE—The purpose of this study was to assess the efficacy of an insulin priming dose with a continuous insulin infusion versus two continuous infusions without a priming dose

The Use of Dietary Additives in Fish Stress Mitigation: Comparative Endocrine and Physiological Responses

In the last years, studies on stress attenuation in fish have progressively grown. This is mainly due to the interest of institutions, producers, aquarists and consumers in improving the welfare of farmed fish. In addition to the development of new technologies to improve environmental conditions of cultured fish, the inclusion of beneficial additives in the daily meal in order to mitigate the stress response to typical stressors (netting, overcrowding, handling, etc.) has been an important research topic. Fish are a highly diverse paraphyletic group (over 27,000 species) though teleost infraclass include around 96% of fish species. Since those species are distributed world-wide, a high number of different habitats and vital requirements exist, including a wide range of environmental conditions determining specifically the stress response. Although the generalized endocrine response to stress (based on the release of catecholamines and corticosteroids) is detectable and therefore provides essential information, a high diversity of physiological effects have been described depending on species. Moreover, recent omics techniques have provided a powerful tool for detecting specific differences regarding the stress response. For instance, for transcriptomic approaches, the gene expression of neuropeptides and other proteins acting as hormonal precursors during stress has been assessed in some fish species. The use of different additives in fish diets to mitigate stress responses has been deeply studied. Besides the species factor, the additive type also plays a pivotal role in the differentiation of the stress response. In the literature, several types of feed supplements in different species have been assayed, deriving in a series of physiological responses which have not focused exclusively on the stress system. Immunological, nutritional and metabolic changes have been reported in these experiments, always associated to endocrine processes. The biochemical nature and physiological functionality of those feed additives strongly affect the stress response and, in fact, these can act as neurotransmitters or hormone precursors, energy substrates, cofactors and other essential elements, implyingmulti-systematic and multi-organic responses. In this review, the different physiological responses among fish species fed stress-attenuating diets based on biomolecules and minerals have been assessed, focusing on the endocrine regulation and its physiological effects

National survey of the management of Diabetic Ketoacidosis (DKA) in the UK in 2014

AIM: To examine, in a national survey, the outcomes of adult patients presenting with DKA in 2014, mapped against accepted UK national guidance.  METHODS: Data were collected in a standardized form covering clinical and biochemical outcomes, risk and discharge planning. The form was sent to all UK diabetes specialist teams (n = 220). Anonymized data were collected on five consecutive patients admitted with DKA between 1 May 2014 and 30 November 2014.  RESULTS: A total of 283 forms were received (n = 281 patients) from 72 hospitals, of which 71.4% used the national guidelines. The results showed that 7.8% of cases occurred in existing inpatients, 6.1% of admissions were newly diagnosed diabetes and 33.7% of patients had had at least one episode of DKA in the preceding year. The median times to starting 0.9% sodium chloride and intravenous insulin were 41.5 and 60 min, respectively. The median time to resolution was 18.7 h and the median length of hospital stay was 2.6 days. Significant adverse biochemical outcomes occurred, with 27.6% of patients developing hypoglycaemia and 55% reported as having hypokalaemia. There were also significant issues with care processes. Initial nurse-led observations were carried out well, but subsequent patient monitoring remained suboptimal. Most patients were not seen by a member of the diabetes specialist team during the first 6 h, but 95% were seen before discharge. A significant minority of discharge letters to primary care did not contain necessary information.  CONCLUSION: Despite widespread adoption of national guidance, several areas of management of DKA are suboptimal, being associated with avoidable biochemical and clinical risk

Acidosis: The Prime Determinant of Depressed Sensorium in Diabetic Ketoacidosis

OBJECTIVE — The etiology of altered sensorium in diabetic ketoacidosis (DKA) remains unclear. Therefore, we sought to determine the origin of depressed consciousness in DKA. RESEARCH DESIGN AND METHODS — We analyzed retrospectively clinical and biochemical data of DKA patients admitted in a community teaching hospital. RESULTS — We recorded 216 cases, 21 % of which occurred in subjects with type 2 diabetes. Mean serum osmolality and pH were 304 31.6 mOsm/kg and 7.14 0.15, respectively. Acidosis emerged as the prime determinant of altered sensorium, but hyperosmolarity played a synergistic role in patients with severe acidosis to precipitate depressed sensorium (odds ratio 2.87). Combination of severe acidosis and hyperosmolarity predicted altered consciousness with 61 % sensitivity and 87 % specificity. Mortality occurred in 0.9 % of the cases. CONCLUSIONS — Acidosis was independently associated with altered sensorium, but hy-perosmolarity and serum “ketone ” levels were not. Combination of hyperosmolarity and acidosis predicted altered sensorium with good sensitivity and specificity. Diabetes Care 33:1837–1839, 2010 D iabetic ketoacidosis (DKA) is fre-quently associated with alteredmental status, which is correlated with the severity of the disease and prog-nosis (1). However, the etiology of de-pressed sensorium in DKA remains uncertain and controversial (2,3). Puta-tive factors in the pathogenesis of diabetic ketoacidotic coma include cerebral hypo-perfusion due to circulatory collapse and cerebral thrombosis (4), reduced cerebral glucose and oxygen utilization (1,5), aci-dosis (6,7), hyperosmolarity (8,9), and direct toxic effect of ketone bodies (2). Cerebral edema remains an important precipitant of altered consciousness in DKA, especially in children. Different studies have yielded con-flicting results regarding the role of these etiologic factors in the pathogenesis of al-tered mentation in patients with DKA. Hence, the origin of clouded sensorium in DKA remains to be fully elucidated. We undertook to study the etiology of de-pressed consciousness in patients admit-ted with DKA at the Regional Medica

Diabetic retinopathy: current and future methods for early screening from a retinal hemodynamic and geometric approach

Diabetic retinopathy (DR) is a major disease and is the number one cause of blindness in the UK. In England alone, 4200 new cases appear every year and 1280 lead to blindness. DR is a result of diabetes mellitus, which affects the retina of the eye and specifically the vessel structure. Elevated levels of glucose cause a malfunction in the cell structure, which affects the vessel wall and, in severe conditions, leads to their breakage. Much research has been carried out on detecting the different stages of DR but not enough versatile research has been carried out on the detection of early DR before the appearance of any lesions. In this review, the authors approach the topic from the functional side of the human eye and how hemodynamic factors that are impaired by diabetes affect the vascular structur

Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA

Severe Hypertriglyceridemia in Diabetic Ketoacidosis Accompanied by Acute Pancreatitis: Case Report

We report a case of diabetic ketoacidosis (DKA) and hypertriglyceridemia (severely elevated to 15,240 mg/dL) complicated by acute pancreatitis, which was treated successfully with insulin therapy and conservative management. A 20-yr-old woman with a history of type 1 diabetes came to the emergency department 7 months after discontinuing insulin therapy. DKA, severe hypertriglyceridemia and acute pancreatitis were diagnosed, with DKA suspected of contributing to the development of the other conditions. In Korea, two cases of DKA-induced hypertriglyceridemia and 13 cases of hypertriglyceridemia-induced acute pancreatitis have been previously reported separately