Sick-day management in type 1 diabetes.

Illness and stress are common occurrences. For the person with type 1 diabetes, these events can be triggers for counterregulation and [table: see text] subsequent metabolic deterioration if there is no attention to diabetes management tasks. Sick-day management requires increased monitoring of blood glucose and assessment for ketosis. Although urine testing for ketones has been the standard approach to sick-day management, new technology for self-monitoring of blood 3HB levels is now available. According to the American Diabetes Association, blood measurement of 3HB "may offer a useful alternative to urine ketone testing." This new technology may provide an opportunity to improve the management of uncontrolled diabetes and sick days in an attempt to reduce the human and economic burden of DKA.     

Correlation between urine ketones (acetoacetate) and capillary blood ketones (3-beta-hydroxybutyrate) in hyperglycaemic patients

AIMS: To facilitate the transition from urine ketones (acetoacetate) to capillary blood ketones (3-beta-hydroxybutyrate), we studied the correlation between these two tests. METHODS: Retrospective study of all patients with blood glucose greater than or equal to 2.5 g/l on arrival in the Emergency Department. We studied the correlation between urine ketones (Clinitek 50, Bayer) and capillary blood ketones (Optium, Abbott). We then compared the relative risks (RR) of ketoacidosis and hospitalization associated with each of these tests. RESULTS: In 33 months, 529 adult patients with both urine and blood testing for ketones were enrolled (ketoacidosis 8%, admission rate 49%). Urine ketones scored as +, ++ and +++ corresponded to median capillary blood ketone levels of 0.5 mmol/l (IQR: 0.1-0.9), 0.7 mmol/l (IQR: 0.2-1.8) and 3 mmol/l (IQR: 1.4-5.2), respectively. RRs of ketoacidosis or hospitalization associated with blood ketones greater than or equal to 3 mmol/l were higher than those associated with +++ urine ketones: 74 (95% confidence interval [CI]: 48-88) and 2.9 (95% CI: 2.5-3) versus 31 (95% CI: 18-45) and 2 (95% CI: 1.7-2.1), respectively. CONCLUSIONS: In hyperglycaemic patients in the Emergency Department, a good correlation was observed between urine ketones and capillary blood ketones for low values, but a poor correlation was observed for high values. Either test can therefore be used to exclude ketosis, but the capillary blood ketones test is more accurate to confirm ketoacidosis.     

Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes

Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies.     

Screening for ketonemia in patients with diabetes.

STUDY OBJECTIVES: To determine the sensitivity and specificity of the urine ketone dip test as a screening test for ketonemia in hyperglycemic patients and to compare the performance of the urine ketone dip test with the anion gap and serum bicarbonate level. METHODS: This was a prospective study conducted in an urban, university-affiliated public hospital emergency department. Inclusion criteria consisted of (1) patients with known diabetes and hyperglycemia (glucose level>200 mg/dL) and any complaint of illness, or (2) patients with hyperglycemia and symptoms of undiagnosed diabetes mellitus. Urine ketone dip test, serum ketone, and electrolyte levels were determined on all subjects. Sensitivity, specificity, and predictive values along with 95% confidence intervals (CIs) were calculated. RESULTS: The study group comprised 697 patients, including 98 patients with diabetic ketoacidosis (DKA) and 88 with diabetic ketosis (DK). The sensitivity, specificity, positive, and negative predictive values of the urine ketone dip test for the detection of DKA were 99% (95% CI 97% to 100%), 69% (95% CI 66% to 73%), 35% (95% CI 29% to 41%), and 100% (95% CI 99% to 100%), respectively. For DKA and DK, the sensitivity, specificity, positive, and negative predictive values of the urine ketone dip test were 95% (95% CI 90% to 97%), 80% (95% CI 76% to 83%), 63% (95% CI 57% to 69%) and 98% (95% CI 96% to 99%). The anion gap and serum bicarbonate level were less sensitive but more specific than the urine ketone dip test for the detection of DKA and DK. CONCLUSION: The urine ketone dip test has high sensitivity for detecting DKA and a high negative predictive value for excluding DKA in hyperglycemic patients with diabetes with any symptoms of illness. The urine ketone dip test is a better screening test for DKA and DK than the anion gap or serum bicarbonate.     

Point of care blood ketone testing of diabetic patients in the emergency department

The aim of our study was to determine the utility of point-of-care blood ketone testing in diabetic patients presenting to the emergency department. In this prospective, observational clinical study, patients with known or newly diagnosed diabetes mellitus presenting to our tertiary care university emergency department with any nontrauma related medical complaint and a high fingerstick glucose (> or =200 mg/dL) were eligible for inclusion. Capillary blood beta-hydroxybutyrate (beta-HBA), venous blood beta-HBA level, venous blood glucose level, arterial blood gas analysis, and urine ketone dipstickstick were measured in each patient as primary outcome measures. Of the 479 diabetic patients presenting during the study period, a total of 139 diabetic patients with high capillary blood glucose level (> or =200 mg/dL) and a positive capillary blood beta-HBA (> or =0.1 mmol/L) were included in the study. Hyperketonemia (> or =0.42 mmol/L) was found in 48 of these patients by Sigma Diagnostics reference testing (diabetic ketosis in 35%). The calculated blood pH was less than 7.3 in 18 of these 48 patients (ketoacidosis in 31%). Capillary and venous blood beta-hydroxybutyrate levels were not statistically different from each other (P = 0.824). There was a positive correlation between capillary and venous blood beta-HBA levels (r = 0.488, P < 0.001). The sensitivity and specificity of urine ketone dipstick testing and capillary blood ketone testing in determining diabetic ketoacidosis were 66% and 78%, and 72% and 82%; and in determining hyperketonemia (both in diabetic ketosis and diabetic ketoacidosis) were 82% and 54%, and 91% and 56%, respectively. A rapid, bedside capillary blood ketone test for beta-HBA can accurately measure blood concentrations of beta-HBA in diabetic patients in an emergency department setting. This device can be used as a reliable diagnostic test to detect emergency metabolic problems in diabetic patients, such as diabetic ketosis or ketoacidosis.     

Urine Ketone Dip Test as a Screen for Ketonemia in Diabetic Ketoacidosis and Ketosis in the Emergency Department

Study objective: To determine the sensitivity of the urine ketone dip test (UKDT) for the detection of ketonemia in patients with diabetic ketoacidosis (DKA) and diabetic ketosis (DK) in the ED. Methods: We conducted a retrospective chart review in the ED of an urban, university- affiliated county teaching hospital. The study population comprised patients seen in the ED during 1994 and 1995 with a discharge diagnosis of DKA or DK and underwent urinalysis within 4 hours of the initial serum electrolyte and ketone determinations. We calculated test sensitivity, along with 95% confidence intervals (CIs). Results: One hundred forty-eight patients with 223 occurrences diagnosed as DKA or DK were seen in the ED during the study period. One hundred fourteen patients with 146 occurrences of DKA or DK met all inclusion criteria; these patients made up the study group. There were 99 cases of DKA and 47 cases of DK. The sensitivity of the UKDT for the detection of ketonemia in all patients with DKA or DK was 97% (95% CI, 94% to 99%) . In the subgroup of patients with DKA, the sensitivity of the UK was 97% (95% CI, 92% to 99%). For patients with DK, the sensitivity of the UK was 98% (95% CI, 89% to 99%). Conclusion: The UKDT is highly sensitive for the presence of serum ketones in patients with DKA and DK. Prospective study is suggested to determine the specificity of the UKDT in this application and to validate its use as a screening tool for the detection of ketonemia in DKA and DK. [Hendey GW, Schwab T, Soliz T: Urine ketone dip test as a screen for ketonemia in diabetic ketoacidosis and ketosis in the emergency department. Ann Emerg Med June 1997; 29:735-738.]     

The hospital and home use of a 30-second hand-held blood ketone meter: guidelines for clinical practice.

AIMS: To establish the role of the measurement of beta-hydroxybutyrate (beta-OHB) in distinguishing simple hyperglycaemia from ketosis, and as an indicator of adequate resolution of ketoacidosis, using an electrochemical blood ketone meter. The aim of the study is to assess the accuracy and precision of the meter and to develop clinical guidelines for the use of the ketone meter at home and in hospital. PATIENTS AND METHODS: Twenty patients with poor glycaemic control (mean HbA1c 10.2%) were recruited from the diabetes clinic and 14 patients admitted with diabetic ketoacidosis (DKA) were recruited from two Accident and Emergency Departments. The blood obtained at each routine fingerprick test for glucose measurement was tested for beta-OHB using the ketone meter. Plasma beta-OHB concentrations were also measured on admission using a laboratory enzymatic method. RESULTS: Paired glucose and beta-OHB meter readings (n = 1099) in clinic patients demonstrated that, in the absence of intercurrent illness, beta-OHB levels did not exceed 1 mmol/l, irrespective of glucose readings. In the 14 ketoacidotic patients, the mean plasma beta-OHB concentration, measured in the laboratory, on admission was 7.4 mmol/l (range 3.9-12.3 mmol/l). The median half-life of beta-OHB was 1.64 h (1st IQR 2.27 h, 3rd IQR 1.34 h). The median time taken, from the initiation of treatment, for beta-OHB concentrations to fall to below 1 mmol/l was 8.46 h (range 5-58.33 h). CONCLUSION: Near patient blood ketone testing is a useful adjunct to blood glucose monitoring in distinguishing between ketosis and simple hyperglycaemia. The data suggest that beta-OHB levels > or = 1 mmol/l require further action and levels > 3 mmol/l necessitate medical review. In addition, the rate of fall of beta-OHB in DKA can be used as an indicator of the adequacy of treatment.     

综合急救处理对糖尿病酮症酸中毒患者的应用价值

目的研究急诊综合急救治疗方法在糖尿病酮症酸中毒治疗上的临床价值。方法将2017年3月—2020年3月于该院急诊科接受治疗的100例糖尿病酮症酸中毒患者作为主要对象,用随机数字表法对其分组,各50例。对照组采用急诊常规急救方法,观察组在常规急救基础上使用胰岛素泵治疗,对比两种处理方法的临床疗效。结果相比于对照组,观察组的治疗总有效率更高,差异有统计学意义(P<0.05);观察组治疗后的空腹血糖和餐后2 h血糖均显著低于对照组,差异有统计学意义(P<0.05);观察组的血酮转阴时间、尿酮转阴时间和血糖达标时间更短,差异有统计学意义(P<0.05)。结论对糖尿病酮症酸中毒患者开展综合急救处理更有利于提高救治有效率,可缩短患者的血酮和尿酮转阴时间,使血糖在短时间内达标,优势显著,值得进一步推广应用。     

Near patient blood ketone measurements and their utility in predicting diabetic ketoacidosis.

AIM: To assess the utility of near patient blood ketone measurements in predicting diabetic ketoacidosis (DKA) among a group of hyperglycaemic unwell patients presenting to a hospital emergency department. METHODS: Near patient blood beta-hydroxybutyrate (beta-OHB) testing has recently been introduced as a new tool in our hospital Accident and Emergency department (A&E) for patients with a finger-prick glucose of > 11 mmol/l. We reviewed the records of the first 50 patients to have a beta-OHB measurement to establish if they developed DKA or received treatment with intravenous insulin within 48 h of presentation. We then compared the diagnostic power of beta-OHB measurements with other clinical, physiological and biochemical markers of DKA. RESULTS: Nine patients had DKA, eight had a compensated metabolic acidosis secondary to raised serum ketones, and 33 had no evidence of DKA during the following 48 h. The median (range) beta-OHB levels in each group were 6.0 (3.1-6.0) mmol/l, 3.4 (1.2-5.7) mmol/l, and 0.1 (0.0-1.2) mmol/l, respectively. A beta-OHB level of > or = 3.0 mmol/l had a sensitivity of 100% and specificity of 88% for DKA. All those with beta-OHB level > 3.0 mmol/l required treatment with intravenous insulin. CONCLUSION: Measuring beta-OHB when a hyperglycaemic patient is identified could offer a simple method of identifying at an early stage those patients at highest risk of DKA (beta-OHB > 3.0 mmol/l), and redirecting the search for a diagnosis in others (beta-OHB < 1.0 mmol/l).     

Comparison of capillary blood ketone measurement by electrochemical method and urinary ketone in treatment of diabetic ketosis and ketoacidosis in children

We aimed to compare the recent practical method of capillary β-hydroxy butyrate (βOHB) measurement with the widely used urinary ketone measurement in monitoring metabolic status of the patient during treatment of diabetic ketoacidosis (DKA) and diabetic ketosis (DK). Patients with DKA and DK admitted to the hospital were followed with simultaneous measurements of capillary βOHB by electrochemical method (Medisense Optium, Abbott), and urinary ketone by semi-quantitative method. Blood gases were measured in 2–4 h intervals. Fourteen patients with DKA/DK (7 males and 7 females, age: 9.2 ± 4.2 years) were included with 50 simultaneous measurements of capillary and urinary ketone. No correlation was detected between urinary ketone and blood pH (P = 0.06) and HCO₃ (P = 0.79), whereas a significant negative correlation was found between capillary βOHB and blood pH (r = −0.41, P < 0.05) and HCO₃ (r = −0.35, P < 0.05). Capillary βOHB and urinary ketone levels did not correlate at the beginning and 3.3 ± 1.4 h after treatment, but did correlate in the third samples taken 7.8 ± 2.0 h after treatment (r = 0.8, P < 0.05). Capillary βOHB levels show good correlation with the degree of acidosis (pH and HCO₃). Capillary βOHB measurement is more sensitive than urinary ketone measurement in reflecting the patient’s metabolic status and improvement during treatment.     

比较血清β-羟丁酸和尿酮体在糖尿病酮症诊断中的意义

目的比较血清β-羟丁酸和尿酮体的检测在糖尿病酮症诊断中的一致性、特异性和敏感性。方法215例糖尿病患者,其中糖尿病非酮症组52例,糖尿病酮症组患者163例,包括单纯酮症患者125例,酮症酸中毒患者38例。同时进行血清β-羟丁酸和尿酮体的检测,并对酮症组患者治疗后复查,直至酮症消失,观察治疗过程中两者的变化情况,共计观察309例次。结果非酮症组有13.5％的患者β羟丁酸增高;309例次的检测中,共计65次尿酮体与血β羟丁酸结果不统一,其中非DK组有7例尿酮体为阴性而血β羟丁酸为阳性。DK组共58例次不统一,其中49例次表现为尿酮体转阴,而血β羟丁酸仍为阳性,9例次表现为尿酮体为阳性,而血β羟丁酸为阴性。结论单纯尿酮体检测对糖尿病酮症的诊断有一定漏诊率,血清伊羟丁酸对糖尿病酮症的检测更敏感,更准确。     

Performance of the continuous glucose monitoring system (CGMS) during development of ketosis in patients on insulin pump therapy.

AIMS: Ketoacidosis is one of the most severe complications of Type 1 diabetes. Development of ketosis leads to substantial shifts in electrolyte and ion concentrations in the different fluid compartments of the body. This study was performed to investigate the performance of the continuous glucose monitoring device (CGMS) during ketoacidosis. METHODS: Twelve patients with Type 1 diabetes using continuous subcutaneous insulin infusion (CSII) participated in this trial [10 women, two men; age (mean +/- sd) 34 +/- 9 years; disease duration 17 +/- 10 years; HbA(1c) 7.1 +/- 1.0%]. In the morning, patients ate breakfast and the insulin pump was stopped at 11.00 h and restarted after 8 h. Observation parameters during this experiment were: blood glucose (laboratory reference and CGMS), 3-hydroxy-butyrate (3-OHB), pH, Na, pCO(2), pO(2), free fatty acids, osmolarity, standard bicarbonate, and lactate. RESULTS: Blood glucose increased and reached a plateau within 2 h after pump stop (from 6.2 +/- 2.56 to 16.7 +/- 4.44 mmol/l, P < 0.001). A constant increase in 3-OHB (from 0.0 to 0.8 +/- 0.5 mmol/l, P < 0.001) and decrease in pH (from 7.43 +/- 0.02 to 7.40 +/- 0.03, P < 0.05) indicated ketosis development. Na decreased from 141 +/- 1.4 to 138 +/- 2.8 mmol/l, P < 0.001). Free fatty acids increased from 0.577 +/- 0.330 to 1.330 +/- 0.462 mmol/l (P < 0.001). The CGMS values showed excellent agreement with the capillary blood laboratory method during the entire experiment, and a modified error grid analysis revealed that 99.5% of the values were in the clinically acceptable zones A and B. CONCLUSION: The CGMS device was confirmed to be reliable and accurate during the development of hyperglycaemia and ketotic conditions.     

Clinical characteristics of diabetic ketoacidosis in users and non-users of SGLT2 inhibitors

AimThis study investigated the clinical characteristics of diabetic ketoacidosis (DKA) and compared the DKA characteristics between patients treated with and without SGLT2 inhibitors.MethodsData were collected from patients aged ≥ 18 years admitted for DKA at nine centres in Korea between September 2014 and April 2017. The electronic medical records of these subjects were retrospectively reviewed. Based on their history of medications taken before admission, subjects were classified as either users or non-users of SGLT2 inhibitors and their clinical characteristics of DKA were compared.ResultsDuring the study, the main subtype of DKA episodes (n = 523) was identified as type 2 diabetes (51%). Average hospitalization duration was 11 days, and average intensive care unit (ICU) time was 2.5 days. The in-hospital mortality rate was 3%, but no users of SGLT2 inhibitors died during DKA treatment. In patients taking SGLT2 inhibitors (n = 15), DKA manifested at 124 days, on average, after starting the inhibitors (range: 7–380 days). Also, SGLT2 inhibitors users had significantly lower plasma glucose levels (413 mg/dL) compared with non-users (554 mg/dL), and longer ICU stays (4 vs. 2 days; P = 0.019).ConclusionIn this report of recent data on the clinical features of DKA in Korea, patients using SGLT2 inhibitors needed longer treatment in ICUs compared with non-users and had lower levels of blood glucose, whereas DKA associated with SGLT2 inhibitors was rare.     

Possible mechanisms responsible for the rise in plasma vasopressin associated with diabetic ketoacidosis in the rat

The plasma concentration of arginine vasopressin (AVP) is increased in diabetic ketoacidosis (DKA) in man and the rat. Although haemodynamic changes and nausea/emesis may account for the increased secretion of AVP in severe human DKA, they appear not to be responsible in moderate DKA. Streptozotocin-treated rats were studied to investigate other factors possibly involved in the secretion of AVP in DKA. Wistar rats were injected i.p. with streptozotocin (150 mg/kg body weight). Diabetic rats were maintained on 3-4 units protamine-zinc insulin (PZI)/day for 11 days, after which PZI was withdrawn for 3 days in half the rats. The plasma concentration of AVP was greater in rats with DKA than in normal controls (mean 11.4 pmol/l compared with 1.6 pmol/l; P less than 0.05). Rats with DKA had higher plasma osmolality and concentrations of blood glucose, beta-hydroxybutyrate and acetoacetate, but lower plasma carbon dioxide content than diabetic and normal controls (P less than 0.05). There were no differences in plasma levels of sodium, urea or haematocrit between rats with DKA and controls. In a separate study involving the same procedures, daily systolic blood pressure was measured using a tail cuff to occlude arterial inflow to the tail, and subsequent detection of the cuff pressure at which the first arterial pulsation appeared. No significant differences were detected between normal and diabetic rats and rats with DKA. Exponential relationships between plasma osmolality and plasma AVP (correlation coefficient, r = + 0.75; P less than 0.01), and plasma ketone bodies and plasma AVP (r = +0.60; P less than 0.05) were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unrecognized persistence of beta-hydroxybutyrate in diabetic ketoacidosis.

We quantitated serial serum beta-hydroxybutyrate (beta-OHB) levels using the Ketosite method in 9 children with IDDM who were treated for diabetic ketoacidosis (DKA) and compared them to urinary ketone measurements by dipstick. Persistent elevations of serum beta-OHB were seen in six patients when the urine became clear of ketones; five of these patients had a recurrence of ketonuria. We conclude that many patients recovering from ketoacidosis have continuing elevations of beta-OHB after the urine is free of ketones and this unrecognized abnormality is the likely cause of recurrence of the ketonuria. We recommend that fluid therapy be continued beyond clearance of ketonuria and suggest using the Ketosite method to document restoration of normal serum beta-OHB levels in patients recovering from DKA.     

Inhibition of ketogenesis by ketone bodies in fasting humans.

Although there exists some indirect evidence that circulating ketone bodies might inhibit their own production rate, the direct demonstration of this homeostatic feed-back phenomenon is still lacking. The present work aims at demonstrating the operation of this control mechanism in human fasting ketosis. Six obese subjects, who fasted 2-23 days, were given a primed constant i.v. infusion of 3- 14C-acetoacetate for 4 hr. After a control period of 2 hr, unlabeled sodium acetoacetate was administered as a primed constant i.v. infusion at the rate of 0.688-1.960 mmol/min until the end of the study. During both periods, the rates of inflow of ketones were estimated from the specific activity of total ketones measured under near isotopic steady state conditions. During the control period, total ketone concentration amounted to 3.98-9.65 mumol/ml and production rates of total ketones ranged between 1.450 and 2.053 mmol/min. The levels of free fatty acids, glycerol, glucose, and insulin averaged respecitvely 1.30 mumol/ml, 0.11 mumol/ml, 74 mg/100 ml, and 5.2 muU/ml. The administration of exogenous ketones during the second phase of the study induced a 47%-92% increase in total ketone levels. During this period, the endogenous production of ketones (calculated as the difference between total inflow rate and acetoacetate infusion rate) amounted only to 67%-90% of control values. Among other factors, this inhibition of ketogenesis was probably partially related to the direct antilipolytic effect of infused ketones. Indeed, there was a concomitant fall in FFA and in glycerol levels averaging respectively 13.5% and 17.3%, without significant changes in peripheral insulin concentrations. Our results demonstrate that during fasting, circulating ketone bodies exert an inhibitory influence on the rate of ketogenesis. This mechanism might play an important role in preventing the development of uncontrolled hyperketonemia during starvation.     

Comparative measurements of glucose, beta-hydroxybutyrate, acetoacetate, and insulin in blood and cerebrospinal fluid during starvation

The possibility that altered central nervous system (CNS) metabolism is reflected by changes in the constituents of the cerebrospinal fluid (CSF) was investigated. From eight obese subjects undergoing total starvation for weight reduction, overnight and 21-day fasting specimens of venous blood and lumbar CSF were obtained nearly simultaneously to determine the concentrations of glucose, beta-hydroxybutyrate (β-OHB), acetoacetate (AcAc), and immunoreactive insulin (IRI). After 21 days of starvation, the glucose concentration fell in both blood and CSF. The decrease in blood glucose was greater than the decline in CSF glucose, resulting in a diminished blood-CSF difference. Concentrations of β-OHB and AcAc in blood and CSF were elevated after prolonged fasting, but blood levels exceeded those in CSF, producing an increased blood-CSF ketone body difference. After an overnight and 21-day fast, the IRI levels in CSF were about one-half of the serum levels. These data suggest that metabolic alterations in CNS metabolism during prolonged starvation are reflected in substrate concentrations observed in CSF, and demonstrate that insulin is presented in the CSF of man.     

Treatment of diabetic ketoacidosis (DKA) with 2 different regimens regarding fluid substitution and insulin dosage (0.025 vs. 0.1 units/kg/h)

Diabetic ketoacidosis (DKA) is still the most dangerous acute complication in type 1 diabetes. The aim of this study was to compare treatment of DKA with a regimen of a low insulin dose (0.025 units/kg/h) vs. a standard insulin dose (0.1 units/kg/h).We retrospectively analysed all cases of children and adolescents (age 0-18 years) with type 1 diabetes and DKA who needed treatment in the ICU in the time period of 1998-2005 in 2 pediatric diabetes centers. In a chart review of the first 48 h after onset of DKA the following parameters where evaluated: pH, blood glucose, sodium, potassium, and ketones in urine. Consciousness, neurological status and complications such as cerebral edema, hypoglycaemia or hypokalemia were also recorded.23 children were treated in center A (low insulin dose) whereas 41 where treated in center B (standard insulin dose). Mean age of the patients was 8.9 (range 1.58-17.7) and 13.5 years (1.25-17.7) respectively (p=0.134). Mean pH was 7.1 and HCO3 was 9.05 and 7.79 respectively (p=0.122). Initial blood glucose was 26 mmol/l (no difference between the 2 centres). Treatment with the standard insulin dose resulted in a slightly shorter duration of acidosis (8 h in center A, 6.5 h in center B) and a significantly faster normalization of blood glucose (18 h in A, vs. 10.5 h in B) (p<0.005). During the first day we found similar and very low rates of hypoglycaemia. In center B one case of suspected cerebral edema and cerebral infarction occurred.Low dose insulin substitution is as safe as the recommended standard dose in respect to the occurrence of acute complications. Acidosis is broken slightly earlier with the standard dose. Implications of this earlier normalisation of pH remain unclear.     

Metabolic and hormonal effects of muscular exercise in juvenile type diabetics

Summary Metabolic and hormonal effects of muscular exercise were studied in juvenile-type diabetics in relation to the prevailing degree of metabolic control and compared with those in healthy control subjects. Two groups of diabetic patients, one in moderate metabolic control and one in ketosis due to insulin withdrawal, were subjected to a 3 hour bicycle ergometer test of comparable, mild work intensity. In both groups of diabetics the exercise-induced rise in blood lactate was similar, but was significantly higher than in control subjects. Blood alanine levels showed a transient, significant rise in both diabetic groups, but not in controls. Blood concentrations of branch-chained amino acids remained unchanged. In the moderately controlled diabetics, exercise induced a marked fall of blood glucose and increases in blood levels of free fatty acids (FFA), ketone bodies and glucagon, which were comparable to the exercise effects in normal controls. In ketotic diabetics, however, exercise led to an additional rise in blood glucose concentration and to increases in ketone body, glucagon and cortisol levels. Significant correlations were found between the exercise effect on blood glucose and initial blood levels of glucose, FFA, ketone bodies and branch chained amino acids: pre-exercise values of above 325 mg/dl glucose, 1173 mol/l FFA, 2.13 mmol/l ketone bodies and 0.74 mmol/l branch chained amino acids led to increased blood glucose levels on exercise, whereas below these limits glucose fell during the exercise test. These findings seem to be, at least in part, explained by the hypothesis of a permissive effect of insulin during stimulation of muscle glucose uptake by exercise. The increased circulating levels of glucagon and cortisol during exercise in ketotic diabetics might represent additional hyperglycaemic and, probably more important, lipolytic and ketogenic stimuli. The results suggest that in moderately controlled, non-ketotic diabetics blood glucose falls during exercise; in ketotic, relatively insulin deficient patients, muscular activity has adverse metabolic and hormonal effects: a further increase in blood glucose, plasma glucagon and cortisol and a rapid aggravation of ketosis.     

Commentary: SGLT inhibitors in type 1 diabetes: Place in therapy and a risk mitigation strategy for preventing diabetic ketoacidosis - the STOP DKA protocol

In the accompanying article, Goldenberg et al. review the promotion of diabetic ketoacidosis by SGLT2 inihibitors. They have carried out a metanalysis showing a 3.5-fold increase in the risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes under treatment with SGLT2 inhibitors. They make a number of suggestions for attempting to mitigate the risk of DKA in these patients, notably including blood ketone monitoring and the use of supplemental carbohydrates with additional insulin when ketones suggest incipient DKA. Their proposal merits evaluation in a clinical trial involving type 1 diabetes, which should also assess the possible cardiorenal benefits demonstrated with treatment with SGLT2 inhibitors in type 2 diabetes.