Use of capillary ketones monitoring in treatment of mild ketotic crisis in people with ketosis-prone atypical diabetes.

This study was carried out to assess the potential reduction in duration of intensive diabetic ketoacidosis treatment in adults with ketosis-prone atypical diabetes (KPD) when using capillary versus urinary ketones. In this cross-sectional study, we included 20 people with KPD presented at the National Obesity Center of the Yaoundé Central Hospital with hyperglycemic decompensation (random capillary glucose ≥13 mmol/L) and significant ketosis (ketonuria≥++) requiring intensive insulin treatment. In all subjects, intensive insulin treatment was initiated at 10 UI per hour with simultaneous measurement of capillary beta-hydroxybutyrate and ketonuria every 2 hours until disappearance of ketonuria. Time-to-disappearance of urine ketones was compared with the time-to-normalization of capillary ß-hydroxybutyrate concentrations. Subjects were aged 46±13 years with a median duration of diabetes of 1.5 (IQR: 0-2.5) years. On admission, the mean blood glucose was 22.8±5 mmol/L and capillary ketones level was 2.9±2.7 mmol/L. The median time-to-disappearance of ketonuria was 5 (IQR: 3-8) hours compared with the time-to-normalization of capillary ß-hydroxybutyrate of 4 (IQR: 2-6) hours, p=0.0002. The absolute difference in time-to-normalization of ketonuria versus ketonemia was 2 (IQR: 1-3) hours and the relative time reduction of treatment was 32.5%±18.0%. Our results suggested that the use of capillary ketones versus ketonuria would allow a significant reduction in duration of intensive insulin treatment by one third in people with KPD.

Diabetic Ketoacidosis in Adolescents and Children: A Prospective Study of Blood versus Urine Ketones in Monitoring Therapeutic Response.

BACKGROUND: diabetic ketoacidosis (DKA) is a potentially lethal complication of diabetes mellitus (DM). There is no study in Indonesia that compares the much-preferred capillary beta hydroxybutirate (ß-OHB) measurement to urine acetoacetate in monitoring therapeutic response of DKA in adolescents. METHODS: a prospective study of 37 adolescents and children with DKA in Cipto Mangunkusumo Hospital was done between June 2006 and March 2011. The patients were followed until the time of DKA resolution. Hourly measurement of random blood glucose, capillary ß-OHB concentration, and urine ketones were done, while blood gas analysis and electrolyte were measured every four hours. RESULTS: median time to resolution was 21 (9-52) hours. Compared to urine ketones, capillary ß-OHB concentration showed stronger correlation with pH (r= -0,52, p= 0,003 vs r= -0,49, p= 0,005) and bicarbonate level (r=-0,60, p=0.000 vs r= -0.48, p=0.007) during the median time of DKA resolution. All capillary ß-OHB measurement yielded negative results at median time of DKA resolution, while urine ketones were still detected up to 9 hours after resolution. CONCLUSION: blood ketone concentration showed better correlation with pH and bicarbonate level, as a tool to monitor therapeutic response in DKA in adolescent, compared to traditional urine ketones test in adolescents.

Old and new approaches to the interpretation of acid-base metabolism, starting from historical data applied to diabetic acidosis.

The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.

Utility of ketone measurement in the prevention, diagnosis and management of diabetic ketoacidosis.

Ketone measurement is advocated for the diagnosis of diabetic ketoacidosis and assessment of its severity. Assessing the evidence base for ketone measurement in clinical practice is challenging because multiple methods are available but there is a lack of consensus about which is preferable. Evaluating the utility of ketone measurement is additionally problematic because of variability in the biochemical definition of ketoacidosis internationally and in the proposed thresholds for ketone measures. This has led to conflicting guidance from expert bodies on how ketone measurement should be used in the management of ketoacidosis. The development of point-of-care devices that can reliably measure the capillary blood ketone ß-hydroxybutyrate (BOHB) has widened the spectrum of applications of ketone measurement, but whether the evidence base supporting these applications is robust enough to warrant their incorporation into routine clinical practice remains unclear. The imprecision of capillary blood ketone measures at higher values, the lack of availability of routine laboratory-based assays for BOHB and the continued cost-effectiveness of urine ketone assessment prompt further discussion on the role of capillary blood ketone assessment in ketoacidosis. In the present article, we review the various existing methods of ketone measurement, the precision of capillary blood ketone as compared with other measures, its diagnostic accuracy in predicting ketoacidosis and other clinical applications including prevention, assessment of severity and resolution of ketoacidosis.

Ketonemia and ketonuria in gestational diabetes mellitus.

BACKGROUND: The use of capillary blood 3-ß-hydroxybutyrate (3HB) is a more precise method than urine ketones measurement for the diagnosis of diabetic ketoacidosis. Fasting ketonuria is common during normal pregnancy, while there is evidence that it is increased among pregnant women with Gestational Diabetes Mellitus (GDM) who are on a diet. 3HB levels have been related to impaired offspring psychomotor development. Reports with concomitant measurement of blood and urine ketones in women with GDM who followed a balanced diet are lacking. OBJECTIVE: To compare the prevalence of fasting ketonemia and ketonuria in women with GDM following the Institute of Medicine diet instructions and assess their possible relation with metabolic parameters and therapeutic interventions. RESEARCH DESIGN AND METHODS: 180 women with GDM were studied. In each patient, in successive visits, capillary blood and urine ketones were simultaneously measured. The total measurements were 378, while the average number of measurements per patient was 2.1. RESULTS: The prevalence of ketonuria was significantly higher than that of ketonemia (x(2)=21.33, p <0.001). Significantly higher mean 3HB levels were observed with respect to ketonuria severity (p=0.001). Bedtime carbohydrate intake was associated with significantly lower 3HB levels (p=0.035). Insulin treatment was associated with significant 3HB levels reduction (p=0.032). Body weight reduction per week between two serial visits was associated with increased 3HB levels (p=0.005). Multiple linear regression analysis showed that weight loss remained the only independent predictor of 3HB levels. CONCLUSIONS: The presence of ketonemia was significantly lower than the presence of ketonuria. Weight loss per week was the only independent factor found to be associated with increased levels of 3HB. The clinical significance of this small increase requires further investigation.

Stroke as the presenting feature of new onset diabetes in a young man.

A 34-year-old man presented to a hospital with a 7-day history of nausea, vertigo, ataxia and frontal headache. Examination revealed ipsilateral cerebellar signs. CT of the brain demonstrated left cerebellar hypodensity suggestive of ischaemic stroke or space occupying lesion. Full blood count showed a markedly raised haemoglobin (219 g/L) and haematocrit (0.56). Admission urinalysis was performed but the results not reviewed. Owing to patient deterioration, an arterial blood gas was performed. This showed profound metabolic acidosis. Repeat urinalysis was positive for glucose and ketones. MRI of the brain confirmed ischaemic stroke. The underlying cause of this was hyperviscosity secondary to relative polycythaemia, resulting from undiagnosed diabetic ketoacidosis as a first presentation of diabetes. This case report highlights ischaemic stroke as an unusual presenting feature of diabetic ketoacidosis. Notably, the underlying diagnosis of diabetic ketoacidosis was initially missed, thereby emphasising the importance of performing an admission urinalysis and acting on the results.

Breath ketone testing: a new biomarker for diagnosis and therapeutic monitoring of diabetic ketosis.

BACKGROUND: Acetone, ß -hydroxybutyric acid, and acetoacetic acid are three types of ketone body that may be found in the breath, blood, and urine. Detecting altered concentrations of ketones in the breath, blood, and urine is crucial for the diagnosis and treatment of diabetic ketosis. The aim of this study was to evaluate the advantages of different detection methods for ketones, and to establish whether detection of the concentration of ketones in the breath is an effective and practical technique. METHODS: We measured the concentrations of acetone in the breath using gas chromatography-mass spectrometry and ß -hydroxybutyrate in fingertip blood collected from 99 patients with diabetes assigned to groups 1 (-), 2 (±), 3 (+), 4 (++), or 5 (+++) according to urinary ketone concentrations. RESULTS: There were strong relationships between fasting blood glucose, age, and diabetic ketosis. Exhaled acetone concentration significantly correlated with concentrations of fasting blood glucose, ketones in the blood and urine, LDL-C, creatinine, and blood urea nitrogen. CONCLUSIONS: Breath testing for ketones has a high sensitivity and specificity and appears to be a noninvasive, convenient, and repeatable method for the diagnosis and therapeutic monitoring of diabetic ketosis.

Ketosis onset type 2 diabetes had better islet ß-cell function and more serious insulin resistance.

Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, ß-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal ß-cell function (HOMA-ß) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P = 0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC(0-0.5), AUC0₋1, AUC0₋3 (P < 0.05). Moreover, this group also had higher HOMA-ß and HOMA-IR than nonketotic group (P < 0.05). From these data, we concluded that ketosis onset T2DM had better islet ß-cell function and more serious insulin resistance than nonketotic onset T2DM.

How sensitive and specific is urinalysis 'dipstick' testing for detection of hyperglycaemia and ketosis? An audit of findings from coronial autopsies.

AIMS: Biochemical analysis of glucose and ketones in the vitreous humour obtained at post-mortem examination is representative of the levels in the blood prior to death. Elevated levels can be indicative of conditions including diabetic ketoacidosis, which can be a cause for unexpected death. A rapid screening test for such conditions can be performed during the autopsy through urinalysis using test strips (urine 'dipstick' testing). The aim of this study was to assess the utility of urinalysis testing for post-mortem detection of derangements of glucose and ketone levels. METHODS: The results of vitreous biochemical analysis and urinalysis were collated from 188 forensic autopsy cases. RESULTS: A vitreous glucose result of above 10 mmol/L was regarded as high. When this was compared to urinalysis results it was found that any urinalysis result above negative had a sensitivity of 0.83 and a specificity of 0.93. A vitreous ketone level of above 5 mmol/L was regarded as significantly elevated; a urinalysis result above negative had a sensitivity of 1, but a specificity of 0.12. CONCLUSIONS: Urinalysis ('dipstick' testing) for glucose has a good sensitivity and specificity for high vitreous glucose levels, which are regarded as indicative of pathological hyperglycaemia during life. It was found that urine testing for ketones either has an excellent sensitivity with low specificity or a poor sensitivity with a good specificity; however, this finding has to be viewed in the context of uncertainty of the biochemical level of significant ketosis.

[Metabolic acidosis in children with newly diagnosed type 1 diabetes and risk factors of urolithiasis]. / Kwasica metaboliczna u dzieci z nowo rozpoznana cukrzyca typu 1 a czynniki ryzyka kamicy moczowej.

INTRODUCTION: Urolithiasis is increasingly being diagnosed in children. Some of the major risk factors for kidney stones are hipercalciuria, hiperoxaluria, hipocitraturia and hydrogen ion content measured by pH. Recently, more and more attention is being paid to the impact of diabetes type 1 and 2 on the development of nephrolithiasis especially in periods of poor metabolic control. AIM OF THE STUDY: was to evaluate the BRI (bonn risk index - rate of spontaneous crystallization of calcium oxalate), the concentration of oxalate, citrate and urine pH in children with acid-base balance disturbances occurring in patients with newly diagnosed type 1 diabetes (DMT1). MATERIAL AND METHODS: The study group included 40 patients aged 6 to 17 years (average age ± SD: 12,58 ± 3,33) with newly diagnosed DMT1. The study was performed twice: at the beginning of the disease, immediately after the treatment of diabetic ketoacidosis (study I) and after obtaining satisfactory metabolic control (study II), that is after about two weeks. The control group consisted of 100 children (6-17 years, average age 12,34 ± 3,96) without symptoms suggestive of urolithiasis. In every child, a 24-hour urine sample was collected. BRI was implemented in the urine by his own semi-micro method. RESULTS: Ionized calcium level was significantly higher immediately after the diagnosis of type 1 diabetes compared to the control group (0,68±0,67 vs. 0,40 ± 0,18 mmol/l; p<0,001) and to study II (0,68 ± 0,67 vs. 0,28 ± 0,23 mmol/l; p=0,008). BRI value was significantly higher in early onset compared to the control group and the study II (3,18 ± 5,54 vs. 0,66 ± 0,52, p<0,001; 3,18 ± 5,54 vs. 0,64 ± 1,56; p=0,034). BRI correlated inversely with pH at admission to the hospital (r=-0,53, p=0,0023). CONCLUSIONS: Metabolic alterations occurring during diabetic ketoacidosis at diagnosis of new type 1 diabetes may predispose to the development of the urinary stones, and thereby to the kidney damage.

Markedly increased serum and urinary fructose concentrations in diabetic patients with ketoacidosis or ketosis.

To investigate fructose concentrations in diabetic patients with ketoacidosis or ketosis, serum fructose concentrations and daily urinary fructose excretion were measured in 23 patients with ketoacidosis (n = 16) and ketosis (n = 7) on the first day of admission. Seventeen patients were diagnosed with type 1, one patient with mitochondrial, and 4 patients with atypical diabetes. In 16 of the 23 patients, serum and urinary fructose could be assessed after starting treatments. Mean serum fructose concentration was 71.6 ± 108.1 µmol/l, and mean daily urinary fructose excretion was 352.1 ± 473.7 µmol/day. Serum fructose levels in patients with atypical diabetes were much higher (205.0 ± 213.3 µmol/l) than those in patients with type 1 diabetes (45.1 ± 44.5 µmol/l), while urinary fructose levels in atypical diabetes (249.7 ± 92.4 µmol/day) tended to be lower than those in type 1 diabetes (382.6 ± 533.2 µmol/day). Serum fructose concentrations decreased significantly (P < 0.05) from 88.1 ± 126.3 to 18.0 ± 11.0 µmol/l, and daily urinary fructose excretion also decreased significantly (P < 0.05) from 459.8 ± 530.9 to 75.1 ± 62.0 µmol/day in accordance with glycemic normalization after treatment. Marked and reversible increases in serum and urinary fructose concentrations were observed in diabetics with ketoacidosis and ketosis.

Diagnostic accuracy of point-of-care testing for diabetic ketoacidosis at emergency-department triage: {beta}-hydroxybutyrate versus the urine dipstick.

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 ß-hydroxybutyrate (ß-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 ß-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, ß-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 ß-OHB and the urine dipstick are equally sensitive for detecting DKA (98.1%). However, ß-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.

Evaluation of a portable meter to measure ketonemia and comparison with ketonuria for the diagnosis of canine diabetic ketoacidosis.

BACKGROUND: The diagnosis of canine diabetic ketoacidosis (DKA) usually is based on measurement of urinary acetoacetate (ketonuria). In humans, this test is less sensitive and specific than blood 3-beta-hydroxybutyrate (ketonemia) evaluation. HYPOTHESIS: Ketonemia measurement using a portable meter is more accurate than ketonuria determination with a dipstick to diagnose canine DKA. ANIMALS: Seventy-two client-owned diabetic dogs with ketonemia, ketonuria, or both. METHODS: Prospective observational study. Based on blood bicarbonate concentration and anion gap, dogs were divided into 2 groups: patients with DKA (n= 25); patients with diabetic ketosis (n= 47). Sensitivity, specificity, and positive and negative likelihood ratio (LR) at different cut-off points were determined for both ketonemia and ketonuria. Receiver operating characteristic (ROC) analysis was used to assess the accuracy of each diagnostic test to diagnose DKA. RESULTS: With regard to ketonemia, cut-off values of 2.3 and 4.3 mmol/L revealed 100% sensitivity and 100% specificity, respectively, whereas cut-off values of 2.8 and 3.5 mmol/L showed a -LR of 0.05 and a + LR of 13.16, respectively. With regard to ketonuria, a cut-off value of 1+ revealed 92% sensitivity, 40% specificity, and -LR of 0.20, whereas a cut-off value of 3+ revealed 44% sensitivity, 94% specificity, and +LR of 6.89. The areas under the ROC curves for the ketonemia and ketonuria tests were significantly different (0.97 and 0.81, respectively, P= .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of ketonemia is accurate and more effective than measurement of ketonuria to diagnose canine DKA.