Sodium glucose cotransporter 2 (SGLT2) inhibitor has been recently reported of diabetic ketoacidosis due to accumulation of ketone bodies in patients with severe dehydration caused from such like diarrhea even though the patient had normal glucose level. This is a case of ketoacidosis in normal glucose level as production of ketone bodies is stimulated in liver with increased secretion of glucagon by stimulation of α cells in pancreas due to increase of lipolysis caused from reducing insulin and by SGLT2 inhibitor among patients who are under concurrent insulin and SGLT2 inhibitor. Thus, insulin dosage reduction requires caution in order to control blood glucose level on combined treatment of SGLT2 inhibitor in a patient who is administering insulin because the patient may be caused ketoacidosis in normal blood glucose level.
Blood Glucose ; Dehydration ; Diabetic Ketoacidosis* ; Diarrhea ; Glucagon ; Glucose* ; Humans ; Insulin* ; Ketone Bodies ; Ketosis ; Lipolysis ; Liver ; Pancreas ; Sodium*

OBJECTIVES: To investigate the risk factors for diabetic ketoacidosis (DKA) in children/adolescents with type 1 diabetes mellitus (T1DM) and to establish a model for predicting the risk of DKA. METHODS: A retrospective analysis was performed on 217 children/adolescents with T1DM who were admitted to General Hospital of Ningxia Medical University from January 2018 to December 2021. Among the 217 children/adolescents,169 cases with DKA were included as the DKA group and 48 cases without DKA were included as the non-DKA group. The risk factors for DKA in the children/adolescents with T1DM were analyzed, and a nomogram model was established for predicting the risk of DKA in children/adolescents with T1DM. RESULTS: For the 217 children/adolescents with T1DM, the incidence rate of DKA was 77.9% (169/217). The multivariate logistic regression analysis showed that high levels of random blood glucose, hemoglobin A1c (HbA1c), blood ketone body, and triglyceride on admission were closely associated with the development of DKA in the children/adolescents with T1DM (OR=1.156, 3.20310¹⁵, 20.131, and 9.519 respectively; P<0.05). The nomogram prediction model had a C-statistic of 0.95, with a mean absolute error of 0.004 between the risk of DKA predicted by the nomogram model and the actual risk of DKA, indicating that the model had a good overall prediction ability. CONCLUSIONS High levels of random blood glucose, HbA1c, blood ketone body, and triglyceride on admission are closely associated with the development of DKA in children/adolescents with T1DM, and targeted intervention measures should be developed to reduce the risk of DKA.
Child ; Adolescent ; Humans ; Diabetes Mellitus, Type 1/complications* ; Blood Glucose ; Glycated Hemoglobin ; Retrospective Studies ; Ketosis ; Risk Factors ; Ketone Bodies ; Triglycerides

Congenital hyperinsulinism (CHI) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia. Hypoglycemia in CHI occurs secondary to the dysregulation of insulin secretion. CHI has been established as a genetic disorder of islet-cell hyperplasia, associated with a mutation of the ABCC8 or KCNJ11 genes, which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel (Kir6.2) subunit of the ATP-sensitive potassium channel, respectively. We report the case of a female newborn infant who presented with repetitive seizures and episodes of apnea after birth, because of hypoglycemia. Investigations revealed hypoglycemia with hyperinsulinemia, but no ketone bodies, and a low level of free fatty acids. High dose glucose infusion, enteral feeding, and medications could not maintain the patient's serum glucose level. Genetic testing revealed a new variation of ABCC8 mutation. Therefore, we report this case of CHI caused by a novel mutation of ABCC8 in a half-Korean newborn infant with diazoxide-unresponsive hyperinsulinemic hypoglycemia.
Apnea ; Blood Glucose ; Brain ; Congenital Hyperinsulinism* ; Enteral Nutrition ; Fatty Acids, Nonesterified ; Female ; Genetic Testing ; Glucose ; Humans ; Hyperinsulinism ; Hyperplasia ; Hypoglycemia ; Infant, Newborn ; Insulin ; Ketone Bodies ; Parturition ; Potassium Channels ; Seizures

PURPOSE: Ketogenic diet (KD) remains a therapy in search of explanation although it is an established treatment for patients with intractable epilepsy. It has been clinically proven more efficacious at younger ages, presumably because of the enhanced ability of the immature brain to extract and utilize ketone bodies. The study was designed to investigate whether ketosis induced by the KD is age-dependent. METHODS: A KD ([fat]:[protein+carbohydrate] ratio of 4.3:1) was administered to male Sprague-Dawley rats for 3 weeks, while control animals were fed a standard rodent chow. Dietary treatment was initiated at either postnatal 3 or 12 weeks. Blood beta-hydroxybutyrate (BHB) levels were assayed from blood obtained via the tail vein with the Keto-SiteTM reflectance meter and test cards on treatment day 21. RESULTS: Blood BHB levels in the KD-treated group were significantly higher than those in the control group in 3 week-old rats (4.18+/-0.62 [n=30] vs. 0.27+/-0.02 [n=30] mM, respectively; p<0.0001) and 12 week-old rats (0.86+/-0.06 [n=30] vs. 0.22+/-0.02 [n=30] mM, respectively; p<0.0001). In the KD-treated groups, blood BHB levels of 3 week-old animals were significantly higher than those of 12 week-old ones (p<0.0001), whereas in the control groups, no significant differences in blood BHB levels between the two age groups (p>0.05). CONCLUSIONS: The present study demonstrates that the KD induces more severe ketosis in younger rats. Age-dependent differences in the degree of ketosis induced by the KD may explain that the diet is clinically more efficacious at younger ages.
3-Hydroxybutyric Acid ; Animals ; Blood Group Antigens ; Brain ; Diet ; Epilepsy ; Humans ; Ketogenic Diet* ; Ketone Bodies ; Ketosis* ; Male ; Rats ; Rats, Sprague-Dawley ; Rodentia ; Veins

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare inborn error of ketone body utilization, characterized by episodic or permanent ketosis. SCOT deficiency is caused by mutations in the OXCT1 gene, which is mapped to 5p13 and consists of 17 exons. A 12-month-old girl presented with severe ketoacidosis and was treated with continuous renal replacement therapy. She had two previously unrecognized mild-form episodes of ketoacidosis followed by febrile illness. While high levels of ketone bodies were found in her blood and urine, other laboratory investigations, including serum glucose, were unremarkable. We identified novel compound heterozygous mutations in OXCT1:c.1118T>G (p.Ile373Ser) and a large deletion ranging from exon 8 to 16 through targeted exome sequencing and microarray analysis. This is the first Korean case of SCOT deficiency caused by novel mutations in OXCT1, resulting in life-threatening ketoacidosis. In patients with unexplained episodic ketosis, or high anion gap metabolic acidosis in infancy, an inherited disorder in ketone body metabolism should be suspected.
Acid-Base Equilibrium ; Acidosis ; Blood Glucose ; Exome ; Exons ; Female ; Humans ; Infant ; Ketone Bodies ; Ketosis ; Metabolism ; Microarray Analysis ; Renal Replacement Therapy ; Transferases

Procalcitonin (PCT) is a newly introduced marker of systemic inflammation and bacterial infection. A marked increase in circulating PCT level in critically ill patients has been related with the severity of illness and poor survival. The goal of this study was to compare the prognostic power of PCT and three other parameters, the arterial ketone body ratio (AKBR), the acute physiology, age, chronic health evaluation (APACHE) III score and the multiple organ dysfunction score (MODS), in the differentiation between survivors and nonsurvivors of systemic inflammatory response syndrome (SIRS). The study was performed in 95 patients over 16 years of age who met the criteria of SIRS. PCT and AKBR were assayed in arterial blood samples. The APACHE III score and MODS were recorded after the first 24 hours of surgical ICU (SICU) admission and then daily for two weeks or until either discharge or death. The patients were divided into two groups, survivors (n=71) and nonsurvivors (n=24), in accordance with the ICU outcome. They were also divided into three groups according to the trend of PCT level: declining, increasing or no change. Significant differences between survivors and nonsurvivors were found in APACHE III score and MODS throughout the study period, but in PCT value only up to the 7th day and in AKBR only up to the 3rd day. PCT values of the three groups were not significantly different on the first day between survivors and nonsurvivors. Receiver operating characteristic (ROC) curves for prediction of mortality by PCT, AKBR, APACHE III score and MODS were 0.690, 0.320, 0.915 and 0.913, respectively, on the admission day. In conclusion, PCT could have some use as a mortality predictor in SIRS patients but was less reliable than APACHE III score or MODS.
*APACHE ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological Markers ; Calcitonin/*blood ; Comparative Study ; Female ; Human ; Ketone Bodies/*blood ; Male ; Middle Aged ; Multiple Organ Failure/blood/diagnosis/*mortality ; Predictive Value of Tests ; Protein Precursors/*blood ; Sepsis Syndrome/blood/diagnosis/*mortality ; Survival Analysis

Fulminant type 1 diabetes mellitus (FT1DM) is a clinical entity in which the process of beta-cell destruction and subsequent progression of hyperglycemia and ketoacidosis are extremely rapid. A 34-year-old woman without any known risk factor for diabetes mellitus experienced a sudden stillbirth at 30 weeks of gestation. She had normal oral glucose tolerance test during pregnancy. Her blood glucose level was 974 mg/dL. Her urine test for ketone bodies was positive. Her hemoglobin A1c level (6.8%) was near normal range at the first emergency room visit. These findings suggested a very recent onset of diabetes mellitus. Her serum C-peptide level was very low. Islet-related autoantibodies were undetectable. Her clinical course, biochemical, and immunological profiles were consistent with FT1DM. After fluid and insulin based management, beta-cell was rescued with insulin therapy during the evolution of FT1D. At 10 days after admission, maintenance dose of insulin was just 8 unit of insulin once daily. This is the first case of FT1DM with robust recovery in insulin secretion in a pregnant woman who had an initial manifestation of 3rd-trimester intrauterine fetal death in Korea.
Adult ; Autoantibodies ; Blood Glucose ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Emergency Service, Hospital ; Female ; Fetal Death* ; Glucose Tolerance Test ; Humans ; Hyperglycemia ; Insulin* ; Ketone Bodies ; Ketosis ; Korea ; Pregnancy ; Pregnant Women* ; Reference Values ; Risk Factors ; Stillbirth

In the well-fed state a relatively high activity of the pyruvate dehydrogenase complex (PDC) reduces blood glucose levels by directing the carbon of pyruvate into the citric acid cycle. In the fasted state a relatively low activity of the PDC helps maintain blood glucose levels by conserving pyruvate and other three carbon compounds for gluconeogenesis. The relative activities of the pyruvate dehydrogenase kinases (PDKs) and the opposing pyruvate dehydrogenase phosphatases determine the activity of PDC in the fed and fasted states. Up regulation of PDK4 is largely responsible for inactivation of PDC in the fasted state. PDK4 knockout mice have lower fasting blood glucose levels than wild type mice, proving that up regulation of PDK4 is important for normal glucose homeostasis. In type 2 diabetes, up regulation of PDK4 also inactivates PDC, which promotes gluconeogenesis and thereby contributes to the hyperglycemia characteristic of this disease. When fed a high fat diet, wild type mice develop fasting hyperglycemia but PDK4 knockout mice remain euglycemic, proving that up regulation of PDK4 contributes to hyperglycemia in diabetes. These finding suggest PDK4 inhibitors might prove useful in the treatment of type 2 diabetes.
Animals ; Blood Glucose ; Carbon ; Citric Acid Cycle ; Diet, High-Fat ; Fasting ; Gluconeogenesis ; Glucose ; Homeostasis ; Hyperglycemia ; Ketone Bodies ; Mice ; Mice, Knockout ; Oxidoreductases ; Phosphoric Monoester Hydrolases ; Phosphotransferases ; Protein Kinases ; Protein-Serine-Threonine Kinases ; Pyruvate Dehydrogenase Complex ; Pyruvic Acid ; Up-Regulation

3-Hydroxybutyric Acid ; blood ; Animals ; Dietary Carbohydrates ; administration & dosage ; Dietary Fats ; administration & dosage ; Dietary Proteins ; administration & dosage ; Disease Models, Animal ; Epilepsy ; diet therapy ; metabolism ; pathology ; Hippocampus ; metabolism ; Kainic Acid ; Ketone Bodies ; metabolism ; Male ; Mossy Fibers, Hippocampal ; pathology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Kainic Acid ; analysis ; genetics