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1.  Hyperglycaemic crises and lactic acidosis in diabetes mellitus 
Postgraduate Medical Journal  2004;80(943):253-261.
Diabetic ketoacidosis, hyperglycaemic hyperosmolar state, and lactic acidosis represent three of the most serious acute complications of diabetes. There have been some advances in our understanding of the pathogenesis of these conditions over the last three decades, together with more uniform agreement on their treatment and innovations in technology. Accordingly their incidence, morbidity, and mortality are decreasing, but at rates that fall short of our aspirations. Hyperglycaemic crises in particular remain an important cause of morbidity and mortality in diabetic populations around the world. In this article, understanding of these conditions and advances in their management, and the available guidelines for their treatment, are reviewed. As far as is possible, the recommendations are based on clear published evidence; failing that, what is considered to be a common sense synthesis of consensus guidelines and recommendations is provided.
doi:10.1136/pgmj.2002.004291
PMCID: PMC1742991  PMID: 15138313
2.  Pancreatic surgery, not pancreatitis, is the primary cause of diabetes after acute fulminant pancreatitis. 
Gut  1992;33(6):843-847.
Acute fulminant pancreatitis is associated with significant morbidity and mortality. To examine the outcome of conservative and surgical treatment of this disorder, 36 patients who survived an initial episode were restudied after a mean of six years. Fifty three per cent had developed diabetes mellitus, half of whom required insulin therapy. Pancreatic resection was associated with a 100% frequency of diabetes, while only 26% of those treated with peritoneal lavage developed this (p less than 0.001). Insulin secretion and sensitivity were assessed using the hyperglycaemic glucose clamp technique. First phase insulin secretion was impaired in surgically treated patients (mean (SEM) 14 (5) microU/ml x 10 minutes) compared with conservatively treated patients and control subjects (144 (66) and 87 (12) microU/ml x 10 minutes, respectively; p less than 0.05). Second phase and 'maximal' insulin secretion were also impaired among the surgically treated patients compared with the conservatively treated patients and the controls. Insulin sensitivity was reduced among the surgically treated patients (2.88 (58) mg/kg.minute) when compared with conservatively treated patients and healthy control subjects (5.87 (1.02) and 6.45 (0.66) mg/kg.minute; p less than 0.05). Pancreatic resection is associated with a very high frequency of diabetes compared with peritoneal lavage, and these results favour conservative treatment of active fulminant pancreatitis whenever possible.
PMCID: PMC1379347  PMID: 1624170
3.  Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study 
Background
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and youth. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV) of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard."
Methods
The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007) in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1) were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA.
Results
Of 30 potential cases, 27 (90%) were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%). Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis.
Conclusions
Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.
doi:10.1186/1471-2288-11-157
PMCID: PMC3235973  PMID: 22112194
4.  Clinical profile and outcomes of adult patients with hyperglycemic emergencies managed at a tertiary care hospital in Nigeria 
Background:
To document the clinical profile and treatment outcomes of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) managed in a tertiary care hospital.
Materials and Methods:
This was a retrospective review of hospital records of patients with DKA and HHS admitted to a tertiary care hospital over a 24-month period. Data on demographics, precipitating factors, clinical features, serum electrolytes, duration of hospital admission, and mortality were extracted.
Results:
Eighty-four patients were included in the study. Fifty (59.5%) were females. Ten (11.9%) persons had type 1 diabetes mellitus (T1DM) and 74 (88.1%) had type 2 diabetes mellitus (T2DM). There were 35 cases of DKA and 49 cases of HHS. Nine patients with T1DM presented in DKA and one in HHS. Forty-eight (55.2%) subjects were previously not diagnosed of diabetes mellitus (DM). The mean±SEM age, casual blood glucose, calculated serum osmolality, and duration of hospital stay of the study subjects were 50.59±1.63 years, 517.98±11.69 mg/dL, 313.59±1.62 mOsmol/L, and 18.85±1.78 days, respectively. Patients with T2DM were significantly older than those with T1DM (54.32±1.34 vs. 23.40±1.38 years, P<0.001).The precipitating factors were poor drug compliance 23 (27.4%), malaria 12 (14.3), urinary tract infection 10 (11.9%), lobar pneumonia 4 (4.8%), and unidentifiable in 29 (34.5%). Common electrolyte derangements were hyponatremia, 31 (36.9%) and hypokalemia 21 (25%). Mortality rate was 3.6%.
Conclusion:
DKA is common in patients with T2DM.Over 50% of the patients presenting with DKA or HHS have no previous diagnosis of DM. Non-compliance, malaria, and infections are important precipitants. Mortality rate is low.
doi:10.4103/0300-1652.104378
PMCID: PMC3531028  PMID: 23293409
Diabetic ketoacidosis; hyperosmolar hyperglycemic state; precipitating factors
5.  Acidosis: The Prime Determinant of Depressed Sensorium in Diabetic Ketoacidosis 
Diabetes Care  2010;33(8):1837-1839.
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 hyperosmolarity and serum “ketone” levels were not. Combination of hyperosmolarity and acidosis predicted altered sensorium with good sensitivity and specificity.
doi:10.2337/dc10-0102
PMCID: PMC2909073  PMID: 20484127
6.  Hyperglycemic emergencies in Indian patients with diabetes mellitus on pilgrimage to Amarnathji yatra 
Background:
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) represent two distinct metabolic derangements manifested by insulin deficiency and severe hyperglycemia, with estimated mortality rates of 2.5–9%. In patients with type 2 diabetes mellitus (DM) controlled by diet or oral agents, DKA does not occur unless there is significant severe stress such as severe sepsis, major surgery, trauma, etc. We observed many such emergencies occurring in pilgrims.
Objective:
We analyzed the data of 13 patients with DM admitted in our endocrine department with hyperglycemic emergencies during 2 years of the annual pilgrimage (yatra) to Amarnathji.
Materials and Methods:
We reviewed and analyzed the case records of 13 yatris with DM who were referred and admitted in our hospital with hyperglycemic emergencies during the yatra season (July–August) of 2006 and 2007.
Results:
Eleven of 13 had DKA and 1 each had HHS and hypoglycemia. After initial clinical assessment and blood sampling for blood counts, electrolytes, blood gases, urinalysis, chest radiography, and electrocardiography, these cases were managed with standard protocol published by American Diabetes Association (ADA) for the management of DKA and HHS. Average blood glucose was 466 mg/dl and nine subjects had moderate to severe ketonuria. All the cases, except one, were in stable condition at the time of discharge.
Conclusion:
High altitude, strenuous exertion of going uphill, withdrawal of insulin or oral hypoglycemic drugs, starvation, sepsis, and alcohol intake were recorded as predisposing factors. Therefore, there is an immense need for institution of a special health education program to all the yatris before taking the endeavor.
doi:10.4103/2230-8210.94267
PMCID: PMC3354951  PMID: 22701854
Amarnath shrine; diabetic ketoacidosis; high altitude climbing; starvation; type 2 diabetes mellitus
7.  Diabetic and endocrine emergencies 
Postgraduate Medical Journal  2007;83(976):79-86.
Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004–5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hypercalcaemia, thyroid storm, myxoedema coma, acute adrenal insufficiency, phaeochromocytoma hypertensive crisis and pituitary apoplexy in the adult population.
doi:10.1136/pgmj.2006.049445
PMCID: PMC2805944  PMID: 17308209
8.  Frequency of Ketoacidosis in Newly Diagnosed Type 1 Diabetic Children 
Oman Medical Journal  2010;25(2):114-117.
Objectives
Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Many patients with newly diagnosed type 1 diabetes present with DKA. The aim of this study is to determine the frequency and the clinical presentation of diabetic ketoacidosis at the diagnosis of type 1 diabetes mellitus in youths in hamadan, Western Province of Iran.
Methods
The Clinical and laboratory data of a total of 200 patients under 19 years of age with newly diagnosed type 1 diabetes mellitus between 1995-2005 were retrospectively reviewed. Statistical analysis was performed using SPSS 11.
Results
48 (24%)of the children were presented in a state of ketoacidosis. Sever form of DKA (pH≤7.2) was observed in 54.5% of patients. The mean age at diagnosis was 7.3±5.15 years in DKA group and 8.59±3.07 in non-DKA group (p=0.22). 60.4% of patient with DKA were female whereas in the non-DKA group, 53.3% of patients were female, the difference was not significant (p=0.38). The duration of symptoms before diagnosis was 14.84±8.19 days in patients with DKA and 22.39±2.27 in the non-DKA group, (p=0.11). No significant difference was found between the age, sex and duration of the symptoms and occurance of DKA. Polydipsia (85.4) polyuria (83.3%), weakness (68.8%) and abdominal pain (52.1%) were the most frequently notified symptoms among the patients. In two cases, diagnosis of DKA was preceded by as appendicitis and the patient underwent appendectomy.
Conclusion
Frequency of DKA at onset of type 1 diabetes mellitus was significant in the studied region. However, it was lower than other regions in Asia. Polydipsia, polyuria, fatigue and abdominal pain were the most common symptoms on presentation.
doi:10.5001/omj.2010.31
PMCID: PMC3215499  PMID: 22125712
9.  Diabetic Ketoacidosis in Type 2 Diabetics: A Novel Presentation of Pancreatic Adenocarcinoma 
Diabetic ketoacidosis (DKA) has been the hallmark of a life-threatening medical emergency for poorly controlled or newly diagnosed type 1 diabetics. In the last two decades, this traditional association has been challenged with increasing reports of type 2 diabetics presenting with DKA. We report the case of a 75-year-old woman with known type 2 diabetes who presented in DKA and was found to have pancreatic adenocarcinoma. A link between diabetes mellitus and pancreatic cancer has been investigated, but the literature remains inconclusive as to whether diabetes mellitus (DM) is a cause or result of pancreatic cancer or simply the confluence of two common entities. Previous case reports of pancreatic tumors presenting with DKA all represented neuroendocrine tumors. Adenocarcinoma of the pancreas should be considered in the list of precipitants for DKA in type 2 DM.
doi:10.1007/s11606-009-1237-9
PMCID: PMC2842543  PMID: 20119682
diabetic ketoacidosis; type 2 diabetics; pancreatic adenocarcinoma
10.  Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique – Skin Autofluorescence 
Mædica  2011;6(4):298-307.
ABSTRACT
Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors. The Autofluorescence Reader may be useful as a clinical tool for rapid assessment of risk for advanced glycation end-products related long-term complications, not only in diabetes, but in other conditions associated with advanced glycation end-products accumulation as well.
PMCID: PMC3391948  PMID: 22879845
advanced glycation end-products; skin autofluorescence; metabolic stess; chronic kidney disease
11.  New Indices for Predicting Glycaemic Variability 
PLoS ONE  2012;7(9):e46517.
Blood glucose variability is known to be associated with increased risk of long-term complications. Reliable indices for predicting hyperglycaemic and hypoglycaemic fluctuations are therefore needed. Glycaemic standard deviation (SD) obtained by continuous glucose monitoring correlates closely with nine previously described glycaemic variability formulas. Here, new indices predictive of glycaemic variability were developed, which can be calculated from laboratory measures based on a single blood draw. The indices included the glycated albumin (GA) to HbA1c ratio (GA/A1c ratio) and the fasting C-peptide immunoreactivity (FCPR) to fasting plasma glucose (FPG) ratio (FCPR index). Predictive values of these indices were assessed in 100 adults with diabetes. GA/A1c ratio and FCPR index showed close associations with glycaemic SD in addition to the nine existing glucose variability formulas. Subjects with a GA/A1c ratio ≥2.8 and FCPR index <3.0 showed the greatest SD and longest durations of hypoglycaemia, while those with a GA/A1c ratio <2.8 and FCPR index ≥3.0 had smaller SDs and little sign of hypoglycaemia. In adults with diabetes, a high GA/A1c ratio and low FCPR index value reflect higher glycaemic excursions, irrespective of diabetes type. Simultaneous measurements of GA, HbA1c, FPG and FCPR may help to identify a group of patients who warrant closer monitoring in relation to glycaemic variability and hypoglycaemia.
doi:10.1371/journal.pone.0046517
PMCID: PMC3459933  PMID: 23029543
12.  Short-term mortality of myocardial infarction patients with diabetes or hyperglycaemia during admission 
Aim: The hypothesis that patients with hyperglycaemia during admission, regardless of previous diagnosis of diabetes, have worse prognosis than those with normal glucose values is controversial. The objective was to assess the role of hyperglycaemia on short-term mortality after myocardial infarction (MI).
Methods and Results: A cohort study nested in a prospective registry of MI patients in the reference hospital of Gerona, Spain was performed. All consecutive MI patients under 75 were registered between 1993 and 1996. Patient and clinical characteristics, including previous diagnosis of diabetes, glycaemia on admission and in the next four days, were recorded. Patients with glycaemia on admission or four day mean glycaemia >6.67 mmol/l were considered hyperglycaemic. The main outcome measure was mortality at 28 days. Of 662 patients with MI included, 195 (29.7%) had previously known diabetes mellitus, but 457 (69.0%) had glycaemia >6.67 mmol/l on admission. Patients with hyperglycaemia on admission were older, more often female, more frequently had a previous diagnosis of diabetes, developed more complications, and had higher 28 day mortality. The effect of admission glycaemia >6.67 mmol/l on 28 day mortality was independent of major confounding factors, particularly previous diagnosis of diabetes (OR=4.20, 95% confidence intervals 1.18 to 14.96).
Conclusions: Higher 28 day mortality was observed among MI patients with glycaemia on admission >6.67 mmol/l compared with patients with lower levels, independently of major confounding variables and, particularly, previous diagnosis of diabetes. This early, simple, and inexpensive marker of bad prognosis after MI should prompt the application of more aggressive treatment of MI and risk factors and, probably, of glycaemia during admission.
doi:10.1136/jech.56.9.707
PMCID: PMC1732251  PMID: 12177090
13.  United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. 
BMJ : British Medical Journal  1995;310(6972):83-88.
OBJECTIVE--To assess the relative efficacy of treatments for non-insulin dependent diabetes over three years from diagnosis. DESIGN--Multicentre, randomised, controlled trial allocating patients to treatment with diet alone or additional chlorpropamide, glibenclamide, insulin, or metformin (if obese) to achieve fasting plasma glucose concentrations < or = 6 mmol/l. SETTING--Outpatient diabetic clinics in 15 British hospitals. SUBJECTS--2520 subjects who, after a three month dietary run in period, had fasting plasma glucose concentrations of 6.1-14.9 mmol/l but no hyperglycaemic symptoms. MAIN OUTCOME MEASURES--Fasting plasma glucose, glycated haemoglobin, and fasting plasma insulin concentrations; body weight; compliance; and hypoglycaemia. RESULTS--Median fasting plasma glucose concentrations were significantly lower at three years in patients allocated to chlorpropamide, glibenclamide, or insulin rather than diet alone (7.0, 7.6, 7.4, and 9.0 mmol/l respectively; P < 0.001) with lower mean glycated haemoglobin values (6.8%, 6.9%, 7.0%, and 7.6%, respectively; P < 0.001). Mean body weight increased significantly with chlorpropamide, glibenclamide, and insulin but not diet (by 3.5, 4.8, 4.8, and 1.7 kg; P < 0.001). A similar pattern was seen for mean fasting plasma insulin concentration (by 0.9, 1.2, 2.4, and -0.1 mU/l; P < 0.001). In obese subjects metformin was as effective as the other drugs with no change in mean body weight and significant reduction in mean fasting plasma insulin concentration (-2.5 mU/l; P < 0.001). More hypoglycaemic episodes occurred with sulphonylurea or insulin than with diet or metformin. CONCLUSION--The drugs had similar glucose lowering efficacy, although most patients remained hyperglycaemic. Long term follow up is required to determine the risk-benefit ratio of the glycaemic improvement, side effects, changes in body weight, and plasma insulin concentration.
PMCID: PMC2548496  PMID: 7833731
14.  Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans 
Diabetic Medicine  2008;25(2):157-164.
Aims
Type 2 diabetes is frequently associated with infectious complications. Swift activation of leucocytes is important for an adequate immune response. We determined the selective effects of hyperglycaemia and hyperinsulinaemia on lipopolysaccharide (LPS)-induced proinflammatory gene expression and cytokine production in leucocytes and on neutrophil functions.
Methods
Six healthy humans were studied on four occasions for 6 h during: (i) lower insulinaemic euglycaemic clamp, (ii) lower insulinaemic hyperglycaemic clamp, (iii) hyperinsulinaemic euglycaemic clamp, and (iv) hyperinsulinaemic hyperglycaemic clamp. Target levels of plasma glucose were 12.0 mmol/l (hyperglycaemic clamps) or 5.0 mmol/l (euglycaemic clamps). Target plasma insulin levels were 400 pmol/l (hyperinsulinaemic clamps) or 100 pmol/l (lower insulinaemic clamps).
Results
Hyperglycaemia reduced LPS-induced mRNA expression of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA), interleukin-1 alpha (IL1A) and chemokine (C-C motif) ligand 3 (CCL3), whereas during hyperinsulinaemia enhanced mRNA levels occurred in six out of eight measured inflammation-related genes, irrespective of plasma glucose levels. Combined hyperglycaemia and hyperinsulinaemia led to enhanced IL1A, interleukin-1 beta (IL1B) and CCL3 mRNA levels upon LPS stimulation. Neither hyperglycaemia nor hyperinsulinaemia altered cytokine protein production, neutrophil migration, phagocytic capacity or oxidative burst activity.
Conclusions
These results suggest that short-term hyperglycaemia and hyperinsulinaemia influence the expression of several inflammatory genes in an opposite direction, that the acute effects of hyperinsulinaemia on inflammatory mRNA levels may be stronger than those of hyperglycaemia, and that the effects of insulin, in particular, may be relevant in the concurrent presence of hyperglycaemia.
Diabet. Med. 25, 157–164 (2008)
doi:10.1111/j.1464-5491.2007.02348.x
PMCID: PMC2268957  PMID: 18290856
cytokines; hyperglycaemia; hyperinsulinaemia; mRNA; neutrophils
15.  Epidemiological characteristics of ketoacidosis among Korean diabetic patients. 
An epidemiological study on diabetic ketoacidosis (DKA) was done by analysis of 207 cases collected from the medical records of 6 major general hospitals in Seoul area during the period of 5 years between 1979 and 1984. There was female predominance in the occurrence of DKA (male/female ratio, 0.71) in spite of the male predominance in general prevalence of diabetes mellitus (1.80). This female predominance in DKA was most striking in the age group under 40. There was a significant seasonal variation in the occurrence of DKA. DKA occurred most frequently in colder season with the highest peak in December. In July and August, the hottest season in Korea, not even a single case of DKA was recorded in this series. No discernible precipitating factor was found in 39.3% of DKA cases and infections was present as a cause of DKA in 30% of cases. In 27.5%, DKA was the first clinical presentation of diabetes and in the remainders of cases, diabetes was known to be present for average of 6.4 years. Mortality of DKA was 13.2% in this series. As to the socioeconomic status, the education level, the style of living and the duration of diabetes, there were not ascertainable differences between the DKA cases and other diabetic cases. The prospective epidemiological study of diabetic population in Korea, especially in female group, would be necessary for elucidation of the characteristics of DKA in Koreans such as the female predominance and the seasonal difference of the occurrence.
PMCID: PMC3053633  PMID: 3151981
16.  The management of diabetic ketoacidosis in children 
Diabetes Therapy  2011;1(2):103-120.
The object of this review is to provide the definitions, frequency, risk factors, pathophysiology, diagnostic considerations, and management recommendations for diabetic ketoacidosis (DKA) in children and adolescents, and to convey current knowledge of the causes of permanent disability or mortality from complications of DKA or its management, particularly the most common complication, cerebral edema (CE). DKA frequency at the time of diagnosis of pediatric diabetes is 10%–70%, varying with the availability of healthcare and the incidence of type 1 diabetes (T1D) in the community. Recurrent DKA rates are also dependent on medical services and socioeconomic circumstances. Management should be in centers with experience and where vital signs, neurologic status, and biochemistry can be monitored with sufficient frequency to prevent complications or, in the case of CE, to intervene rapidly with mannitol or hypertonic saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours; an initial bolus of 10–20 mL/kg 0.9% saline is followed by 0.45% saline calculated to supply maintenance and replace 5%–10% dehydration. Potassium (K) must be replaced early and sufficiently. Bicarbonate administration is contraindicated. The prevention of DKA at onset of diabetes requires an informed community and high index of suspicion; prevention of recurrent DKA, which is almost always due to insulin omission, necessitates a committed team effort.
doi:10.1007/s13300-010-0008-2
PMCID: PMC3138479  PMID: 22127748
adolescents; cerebral edema; children; complications; diabetic ketoacidosis; fluid replacement; hypokalemia; management; prevention; recurrent DKA
17.  The management of diabetic ketoacidosis in children 
Diabetes Therapy  2011;1(2):103-120.
The object of this review is to provide the definitions, frequency, risk factors, pathophysiology, diagnostic considerations, and management recommendations for diabetic ketoacidosis (DKA) in children and adolescents, and to convey current knowledge of the causes of permanent disability or mortality from complications of DKA or its management, particularly the most common complication, cerebral edema (CE). DKA frequency at the time of diagnosis of pediatric diabetes is 10%–70%, varying with the availability of healthcare and the incidence of type 1 diabetes (T1D) in the community. Recurrent DKA rates are also dependent on medical services and socioeconomic circumstances. Management should be in centers with experience and where vital signs, neurologic status, and biochemistry can be monitored with sufficient frequency to prevent complications or, in the case of CE, to intervene rapidly with mannitol or hypertonic saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours; an initial bolus of 10–20 mL/kg 0.9% saline is followed by 0.45% saline calculated to supply maintenance and replace 5%–10% dehydration. Potassium (K) must be replaced early and sufficiently. Bicarbonate administration is contraindicated. The prevention of DKA at onset of diabetes requires an informed community and high index of suspicion; prevention of recurrent DKA, which is almost always due to insulin omission, necessitates a committed team effort.
doi:10.1007/s13300-010-0008-2
PMCID: PMC3138479  PMID: 22127748
adolescents; cerebral edema; children; complications; diabetic ketoacidosis; fluid replacement; hypokalemia; management; prevention; recurrent DKA
18.  Problems of diabetics in prison. 
BMJ : British Medical Journal  1989;298(6668):221-223.
Providing care for diabetics is difficult in prison. Six diabetic prisoners or former prisoners were seen whose care was difficult or unsatisfactory. Three had multiple admissions to hospital during their sentences with diabetic ketoacidosis that they induced themselves by not taking insulin. The motive seemed to be removal from prison to the fairly pleasant surroundings of the local hospital. A fourth prisoner required admission in a hyperglycaemic, hyperosmolar state that had gone unnoticed as he was thought to be "acting up." The two others had imperfect long term management of diabetes during their sentences. There is clearly room for improvement in diabetic services in British prisons, but manipulative behaviour on the part of some diabetic prisoners may remain a problem.
PMCID: PMC1835557  PMID: 2493867
19.  The risk and outcome of cerebral oedema developing during diabetic ketoacidosis 
BACKGROUND—Cerebral oedema is a major cause of morbidity and mortality in children with insulin dependent diabetes.
AIMS—To determine the risk and outcome of cerebral oedema complicating diabetic ketoacidosis (DKA).
METHODS—All cases of cerebral oedema in England, Scotland, and Wales were reported through the British Paediatric Surveillance Unit between October 1995 and September 1998. All episodes of DKA were reported by 225 paediatricians identified as involved in the care of children with diabetes through a separate reporting system between March 1996 and February 1998. Further information about presentation, management, and outcome was requested about the cases of cerebral oedema. The risk of cerebral oedema was investigated in relation to age, sex, seasonality, and whether diabetes was newly or previously diagnosed.
RESULTS—A total of 34 cases of cerebral oedema and 2940 episodes of DKA were identified. The calculated risk of developing cerebral oedema was 6.8 per 1000 episodes of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000) diabetes. There was no sex or age difference. Cerebral oedema was associated with a significant mortality (24%) and morbidity (35% of survivors).
CONCLUSIONS—This first large population based study of cerebral oedema complicating DKA has produced risk estimates which are more reliable and less susceptible to bias than those from previous studies. Our study indicates that cerebral oedema remains an important complication of DKA during childhood and is associated with significant morbidity and mortality. Little is known of the aetiology of cerebral oedema in this condition and we are currently undertaking a case control study to address this issue.


doi:10.1136/adc.85.1.16
PMCID: PMC1718828  PMID: 11420189
20.  Diagnostic Accuracy of Point-of-Care Testing for Diabetic Ketoacidosis at Emergency-Department Triage 
Diabetes Care  2011;34(4):852-854.
OBJECTIVE
In the emergency department, hyperglycemic patients are screened for diabetic ketoacidosis (DKA) via a urine dipstick. In this prospective study, we compared the test characteristics of point-of-care β-hydroxybutyrate (β-OHB) analysis with the urine dipstick.
RESEARCH DESIGN AND METHODS
Emergency-department patients with blood glucose ≥250 mg/dL had urine dipstick, chemistry panel, venous blood gas, and capillary β-OHB measurements. DKA was diagnosed according to American Diabetes Association criteria.
RESULTS
Of 516 hyperglycemic subjects, 54 had DKA. The urine dipstick had a sensitivity of 98.1% (95% CI 90.1–100), a specificity of 35.1% (30.7–39.6), a positive predictive value of 15% (11.5–19.2), and a negative predictive value of 99.4% (96.6–100) for DKA. Using the manufacturer-suggested cutoff of >1.5 mmol/L, β-OHB had a sensitivity of 98.1% (90.1–100), a specificity of 78.6% (74.5–82.2), a positive predictive value of 34.9% (27.3–43), and a negative predictive value of 99.7% (98.5–100) for DKA.
CONCLUSIONS
Point-of-care β-OHB and the urine dipstick are equally sensitive for detecting DKA (98.1%). However, β-OHB is more specific (78.6 vs. 35.1%), offering the potential to significantly reduce unnecessary DKA work-ups among hyperglycemic patients in the emergency department.
doi:10.2337/dc10-1844
PMCID: PMC3064039  PMID: 21307381
21.  Stroke topography and outcome in relation to hyperglycaemia and diabetes. 
In a prospective study to analyse stroke topography and outcome in diabetics and to determine the prognostic value of blood glucose and glycosylated haemoglobin estimation, we evaluated 176 patients with acute stroke. The patients were classified into four groups on the basis of history, fasting glucose, and glycosylated haemoglobin: euglycaemic patients with no history of diabetes, stress hyperglycaemia, newly diagnosed diabetics, and known diabetics. A high prevalence of undiagnosed diabetes was shown. No difference was found in the type or site of stroke between the four groups. No difference was found in the site of symptomatic or incidental lesions on computerised axial tomography. Patients with stress hyperglycaemia and known diabetics had more severe strokes. Mortality was higher in patients with stress hyperglycaemia, newly diagnosed diabetics, and the combined diabetes groups. This increased mortality was evident in the hyperglycaemic and diabetic groups, even after excluding patients with cerebral haemorrhage. Stroke severity and mortality also increased independently with blood glucose in the euglycaemic group. We conclude that there is a correlation between admission glucose concentration, diabetes, and poor stroke outcome, which may not be attributed to stroke type or location.
PMCID: PMC489037  PMID: 1583510
22.  Thyroid storm associated with Graves' disease covered by diabetic ketoacidosis: A case report 
Thyroid Research  2011;4:8.
Background
Thyroid storm is a condition in which multiple organ dysfunction results from failure of the compensatory mechanisms of the body owing to excessive thyroid hormone activity induced by some factors in patients with thyrotoxicosis. While diabetic ketoacidosis (DKA) is an important trigger for thyroid storm, simultaneous development of DKA and thyroid storm is rare.
Case presentation
A 59-year-old woman with no history of either diabetes mellitus or thyroid disease presented to our hospital because of developing nausea, vomiting and diarrhea for 2 days. Physical examination showed mild disturbance of consciousness, fever, and tachycardia. There were no other signs of thyrotoxicosis. Laboratory studies revealed elevation of random blood glucose and glycosylated hemoglobin, strongly positive of urine acetone, and metabolic acidosis. Since DKA was diagnosed, we initiated the patient on treatment with administration of insulin and adequate fluid replacement. Although the hyperglycemia and acidosis were immediately relieved, the disturbance of consciousness and tachycardia remained persistent. Levels of FT3 and FT4 were extremely high and TSH was below the detectable limit. TRAb was positive. The thyroid storm score of Burch & Wartofsky was 75/140, and the thyroid storm diagnostic criteria of the Japan Thyroid Association were satisfied. Oral administration of thiamazole, potassium iodide and propranolol resulted in immediate relief of the tachycardia.
Discussion
We encountered a case of thyroid storm associated with Graves' disease covered by DKA. Thyroid storm and DKA are both potentially fatal, and the prognosis varies depending on whether or not these conditions are detected and treated sufficiently early. The thyroid storm diagnostic criteria prepared in 2008 by the Japan Thyroid Association are very simple as compared to the Burch & Wartofsky scoring system for thyroid storm. The Japanese criteria may be useful in the diagnosis of this condition since they enable clinicians to identify a broad range of cases with thyroid storm. When dealing with cases of DKA or thyroid storm, it seems essential to bear in mind the possibility of the coexistence of these two diseases.
doi:10.1186/1756-6614-4-8
PMCID: PMC3094317  PMID: 21492449
23.  The role of insulin therapy and glucose normalisation in patients with acute coronary syndrome 
Netherlands Heart Journal  2011;19(2):79-84.
Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose–insulin–potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemia improves outcome in patients with AMI, achievement of glucose regulation is difficult and carries the risk of hypoglycaemia. More research is needed to determine the optimal glucose target levels in AMI and to investigate whether computerised glucose protocols and continuous glucose sensors can improve safety and efficacy of IGL.
doi:10.1007/s12471-010-0065-1
PMCID: PMC3040349  PMID: 21461038
Acute coronary syndrome; Unstable angina pectoris; Myocardial infarction; Hyperglycemia; Glucose; Insulin; Potassium; Clinical protocols
24.  The role of insulin therapy and glucose normalisation in patients with acute coronary syndrome 
Netherlands Heart Journal  2011;19(2):79-84.
Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose–insulin–potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemia improves outcome in patients with AMI, achievement of glucose regulation is difficult and carries the risk of hypoglycaemia. More research is needed to determine the optimal glucose target levels in AMI and to investigate whether computerised glucose protocols and continuous glucose sensors can improve safety and efficacy of IGL.
doi:10.1007/s12471-010-0065-1
PMCID: PMC3040349  PMID: 21461038
Acute coronary syndrome; Unstable angina pectoris; Myocardial infarction; Hyperglycemia; Glucose; Insulin; Potassium; Clinical protocols
25.  Modulatory effect of polyphenolic extracts of Ichnocarpus frutescens on oxidative stress in rats with experimentally induced diabetes 
Background & objectives:
The role of oxidative stress in the development of diabetes mellitus and its vascular complications are extensively studied. Hyperglycaemia causes oxidative damage by generation of reactive oxygen species and results in the development of complications. The present study was undertaken with the objective of exploring the anti-hyperglycaemic potential of polyphenolic enriched extract of Ichnocarpus frutescens in streptozotocin induced (n-STZ) neonatal diabetic rats (pups) for six weeks and to study oxidative stress and antioxidant status.
Methods:
Two days old pups were rendered diabetic by single injection of streptozotocin (90 mg/kg body wt, ip). At the end of the treatment period, the level of blood glucose, serum biochemical markers, serum lipid levels and liver malondialdehyde, tissue antioxidant levels were measured.
Results:
A marked rise was observed in the levels of fasting blood glucose (230.33 mg/dl), lipid profiles, lipid peroxidative products and a significant decrease in tissue antioxidants (superoxide dismuatase, catalase and reduced glutathione) and serum high density lipoprotein cholesterol levels in STZ treated rats. Oral administration of polyphenolic extract (150 and 300 mg/kg body wt, po) decreased fasting blood glucose levels (187.66 and 170.50 mg/dl, respectively) of STZ-treated diabetic rats significantly (P<0.01), when compared with control rats. In addition, the polyphenolic extract showed favourable effect (P<0.01) on the reduced tissues antioxidants level, liver glycogen level, high density lipoprotein level, with significant (P<0.01) reduction of elevated lipid peroxidation products. Histopathological study of the pancreas showed the protective role of polyphenolic extract.
Interpretation & conclusions:
Our study showed the antioxidant of effect polyphenolic extract of I. frutescens in STZ induced experimental diabetes. The results also suggested that this polyphenolic rich extract could be potentially useful for hyperglycaemia treatment to correct the diabetic state.
PMCID: PMC3573603  PMID: 23287129
Antioxidants; diabetes mellitus; Ichnocarpus frutescens; neonatal rats; oxidative stress; polyphenolic extract; streptozotocin

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