sodium-bicarbonate and Diabetes-Mellitus--Type-2

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a relatively novel class of oral medications for the treatment of Type 2 DM with a generally acceptable safety profile. However, these agents have been associated with rare events of a serious and potentially life-threatening complication named euglycemic diabetic ketoacidosis (euDKA). euDKA is not identical with the typical diabetic ketoacidosis, as it often presents with serious metabolic acidosis but only mild to moderate glucose and anion gap elevation.. We report a case of a 51-year old female with Type 2 DM treated with an SGLT-2 inhibitor, developing severe metabolic acidosis with only mild blood glucose elevation after a routine surgery. A careful evaluation of involved factors led to the diagnosis of euDKA, followed by cautious application of simple therapeutic measures that resulted in complete restoration of acidosis and glycemic control in less than 48-h.. Euglycemic ketoacidosis is a rare but rather serious complication of SGLT-2 inhibitors use, often with a multifactorial etiology. Its atypical presentation requires a high level of awareness by physicians as early recognition of this complication can quickly and safely restore acid-base balance.

Topics: Acid-Base Equilibrium; Anti-Bacterial Agents; Benzhydryl Compounds; Blood Gas Analysis; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Fluid Therapy; Glucosides; Glycerophosphates; Humans; Hypoglycemic Agents; Hysterectomy; Insulin; Middle Aged; Postoperative Complications; Sodium Bicarbonate; Sodium-Glucose Transporter 2 Inhibitors; Surgical Wound Infection

Topics: Abdominal Pain; Acidosis, Lactic; Aged; Antigens, Neoplasm; Carcinoma; Diabetes Mellitus, Type 2; Drug Resistance; Fatal Outcome; Female; Humans; Hypertension; Ki-1 Antigen; Sodium Bicarbonate; Stomach Neoplasms

Diabetic ketoacidosis is a common, serious acute complication in children with diabetes mellitus. Diabetic ketoacidosis can accompany new-onset type 1 diabetes mellitus or it can occur with established type 1 diabetes mellitus during the increased demands of an acute illness or with decreased insulin delivery due to omitted doses or insulin pump failure. Additionally, diabetic ketoacidosis episodes in children with type 2 diabetes mellitus are being reported with greater frequency. Although the diagnosis is usually straightforward in a known diabetes patient with expected findings, a fair proportion of patients with new-onset diabetes present in diabetic ketoacidosis. The initial management of children with diabetic ketoacidosis frequently occurs in an emergency department. Physicians must be aware that diabetic ketoacidosis is an important consideration in the differential diagnosis of pediatric metabolic acidosis. This review will acquaint emergency medicine clinicians with the pathophysiology, treatment, and potential complications of this disorder.

Topics: Ambulatory Care; Blood Urea Nitrogen; Brain Edema; Child; Contraindications; Creatinine; Critical Pathways; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diagnosis, Differential; Dose-Response Relationship, Drug; Electrolytes; Emergency Medicine; Emergency Service, Hospital; Fluid Therapy; Humans; Hypoglycemic Agents; Insulin; Phosphates; Potassium; Risk Management; Sodium Bicarbonate

To measure the rate of gluconeogenesis in humans directly, one must administer and determine the specific activity or the enrichment in an intermediate in the gluconeogenic process and in the glucose formed, thus obtaining the fraction of the glucose formed by gluconeogenesis. By a separate determination of the rate of hepatic glucose production, the rate of gluconeogenesis can then be calculated. The closer the intermediate is to glucose-6-P, the more complete will be the measurement of the rate. Thus, if the intermediate is below the level of the triose phosphates, gluconeogenesis from glycerol will not be included in the estimate. Estimates of rates of gluconeogenesis from estimates of PEP enrichment or specific activity require a measure of the extent of exchange of label at the level of oxaloacetate. By using 14C or 13C labeled CO2 as the intermediate and estimating the relative rates of the reactions of the tricarboxylic acid cycle relative to gluconeogenesis from the distribution of 14C from [3-14]lactate in glutamine from the glutamine conjugate of phenylacetate, the enrichment or specific activity of PEP has been estimated. Correction must be made for the incorporation into the glutamine of 14CO2 formed from the [3-14C]lactate. Data support the validity of this approach toward estimating gluconeogenesis in NIDDM, but the approach is complex, time consuming and with uncertainties. Estimates that have been made using [2-14C] acetate are invalid because of the extensive metabolism of [2-14C]acetate in other than liver. Other approaches have promise, but technical problems may exist in their use and other problems, such as hepatic zonation and exchange reactions, may compromise their application.

Topics: Acetates; Animals; Carbon Dioxide; Carbon Radioisotopes; Diabetes Mellitus, Type 2; Gluconeogenesis; Humans; Kinetics; Sodium Bicarbonate

Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type-2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or glucose control in non-diabetic older adults. Fasting blood glucose and insulin were measured in stored samples from subjects who had completed a 3-month clinical trial of bicarbonate supplementation to improve indicators of bone and muscle health. One hundred and fifty three ambulatory, non-diabetic adults aged 50 years and older were studied. Subjects were randomized to one of two bicarbonate groups (67.5 mmol/day of potassium bicarbonate or sodium bicarbonate) or to one of two no-bicarbonate groups (67.5 mmol/day of placebo or potassium chloride). Subjects remained on treatment throughout the 3-month study. The primary outcome measures were changes in fasting plasma glucose, serum insulin and HOMA-IR, an index of insulin resistance. Bicarbonate supplementation reduced net acid excretion (adjusted mean±SEM for the change in NAE/creatinine, mmol/mmol, was 0.23±0.22 in the no-bicarbonate group compared with -3.53±0.22 in the bicarbonate group, P<0.001) but had no effect on fasting plasma glucose, serum insulin, or HOMA-IR. In conclusion, bicarbonate supplementation does not appear to improve insulin sensitivity or glucose control in non-diabetic older adults.

Topics: Acidosis; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Placebos; Sodium Bicarbonate; Treatment Failure

An autoregulatory mechanism involving a reciprocal relationship between gluconeogenesis and glycogenolysis regulates endogenous glucose production (EGP) in healthy individuals. In type 2 diabetes, fasting hyperglycemia may be due to increased EGP.. To examine gluconeogenesis and autoregulation of EGP in type 2 diabetes, 9 type 2 diabetics and 8 healthy controls were studied during a 3-h infusion of 30 micromol/kg/min Na-lactate. The diabetics were also studied during a control infusion of Na-bicarbonate. To standardize levels of glucoregulatory hormones, plasma insulin, growth hormone, and glucagon were clamped at identical levels during the three experiments. Glucagon levels were elevated from basal levels to approximately 330 ng/l when the lactate or bicarbonate infusions were started, in order to mimic the hyperglucagonemia often seen in diabetes. Lactate gluconeogenesis and total EGP were measured by infusions of [6-(3)H] glucose and [U-14C] lactate.. In the bicarbonate experiments, hyperglugagonemia increased lactate gluconeogenesis in the diabetic patients from 4.3+/-1.8 to 6.1+/-2.4 micromol/kg/min (p=0.04). EGP did not change significantly (basal EGP: 15.3+/-3.9, EGP at the end of the study: 14.2+/-3.9 micromol/kg/min, p=0.14). During both lactate experiments, plasma lactate increased more than 4-fold. The increase in lactate gluconeogenesis was significantly higher in diabetics than in controls (values obtained at the end of experiments minus basal values: 10.8+/-3.6 versus 6.4+/-3.6 micromol/kg/min, p=0.03). Compared with normal subjects, the diabetic patients had higher EGP values both at basal conditions (p=0.001) and during lactate infusion (p=0.005). Despite augmented gluconeogenesis, EGP did not change during lactate and glucagon infusion in any of the groups (diabetics, basal EGP: 15.4+/-2.7 versus EGP at the end of experiments: 15.6+/-3.6 micromol/kg/min, p>0.30. Controls, basal EGP: 11.8+/-0.8 versus EGP at the end of experiments: 11.6+/-1.9 micromol/kg/min, p>0.30).. Although type 2 diabetics have increased EGP and increased lactate gluconeogenesis, the hepatic autoregulation of EGP during increased substrate-induced gluconeogenesis seems to be intact.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucagon; Gluconeogenesis; Glucose; Glucose Clamp Technique; Homeostasis; Human Growth Hormone; Humans; Insulin; Liver; Male; Middle Aged; Sodium Bicarbonate; Sodium Lactate

Topics: Acidosis, Lactic; Acute Kidney Injury; Aged; Alanine; Continuous Renal Replacement Therapy; Diabetes Mellitus, Type 2; Female; Heart Failure; HIV Infections; Humans; Oliguria; Reverse Transcriptase Inhibitors; Sodium Bicarbonate; Tenofovir

Dapagliflozin (a sodium-glucose cotransporter-2 [SGLT2] inhibitor) represents the most recently approved class of oral medications for the treatment of type 2 diabetes. Dapagliflozin lowers plasma glucose concentration by inhibiting the renal reuptake of glucose in the proximal renal tubules. In 2015, the US Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis in patients taking this medication.. We present the case of a 23-year-old woman with type 2 diabetes treated with dapagliflozin (10 mg, once a day) for 2 years who presented to the emergency department with abdominal pain.. We diagnosed her with severe ketoacidosis with a normal glucose level (177 mg/dL) due to dapagliflozin, accompanying acute pancreatitis due to hypertriglyceridemia. We concluded that the precipitating factor for euglycemic ketoacidosis was pseudomembranous colitis.. She was treated with intravenous infusions of insulin, isotonic saline, and sodium bicarbonate as diabetic ketoacidosis treatment.. She was in shock with severe metabolic acidosis. After continuous renal replacement therapy, the uncontrolled metabolic ketoacidosis was treated, and she is currently under follow-up while receiving metformin (500 mg, once a day) and short- and long-acting insulins (8 units 3 times and 20 units once a day).. We report an unusual case of SGLT2 inhibitor-induced euglycemic ketoacidosis recovered by continuous renal replacement therapy in a patient with type 2 diabetes and recurrent acute pancreatitis due to hypertriglyceridemia. We diagnosed a rare complication of the SGLT2 inhibitor in a patient with type 2 diabetes in whom uncontrolled metabolic ketoacidosis could be effectively managed via continuous renal replacement therapy.

Topics: Adult; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Hypoglycemic Agents; Insulin; Ketosis; Renal Replacement Therapy; Saline Solution; Sodium Bicarbonate; Young Adult

A woman aged 44 underwent elective standard abdominoplasty and bilateral mastopexy (superiorly based pedicle with vertical scar) following weight loss of 8.5 stone (53.9 kg) over a 5-year period. She had type 2 diabetes and her antidiabetic medications included metformin, liraglutide and empagliflozin. Towards the end of the first postoperative day, she reported gradual onset of nausea, vomiting and abdominal pain. Her condition continued to deteriorate overnight, becoming tachycardic and tachypnoeic. Urgent investigations showed severe diabetic ketoacidosis with euglycaemia. She was managed with fluid resuscitation, insulin infusion and intravenous sodium bicarbonate in the high dependency unit. She made a complete clinical and biochemical recovery and was discharged on day 9 postoperatively. This case illustrates a diagnostic challenge of a serious life-threatening complication of diabetes in the postoperative period associated with a novel class of antidiabetic medications, sodium-glucose cotransporter 2 inhibitors.

Topics: Abdominoplasty; Adult; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Humans; Infusions, Intravenous; Inpatients; Insulin; Ketosis; Postoperative Complications; Sodium Bicarbonate

Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin's role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested.

Topics: Acid-Base Equilibrium; Acidosis, Lactic; Biomarkers; Diabetes Mellitus, Type 2; Fatal Outcome; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Renal Dialysis; Sodium Bicarbonate; Treatment Outcome

An intoxication with drugs, ethanol or cleaning solvents may cause a complex clinical scenario if multiple agents have been ingested simultaneously. The situation can become even more complex in patients with (multiple) co-morbidities. A 59-year-old man with type 2 diabetes mellitus (without treatment two weeks before the intoxication) intentionally ingested a substantial amount of ethanol along with ~750 mL of laminate floor cleaner containing citric acid. The patient was admitted with severe metabolic acidosis (both ketoacidosis and lactic acidosis, with serum lactate levels of 22 mM). He was treated with sodium bicarbonate, insulin and thiamine after which he recovered within two days. Diabetic ketoacidosis and lactic acidosis aggravated due to ethanol intoxication, thiamine deficiency and citrate. The high lactate levels were explained by excessive lactate formation caused by the combination of untreated diabetes mellitus, thiamine deficiency and ethanol abuse. Metabolic acidosis in diabetes is multi-factorial, and the clinical situation may be further complicated, when ingestion of ethanol and toxic agents are involved. Here, we reported a patient in whom diabetic ketoacidosis was accompanied by severe lactic acidosis as a result of citric acid and mainly ethanol ingestion and a possible thiamine deficiency. In the presence of lactic acidosis in diabetic ketoacidosis, physicians need to consider thiamine deficiency and ingestion of ethanol or other toxins.

Topics: Acidosis; Acidosis, Lactic; Alcoholic Intoxication; Citric Acid; Diabetes Mellitus, Type 2; Humans; Insulin; Male; Middle Aged; Severity of Illness Index; Sodium Bicarbonate; Thiamine; Thiamine Deficiency

Topics: Acid-Base Equilibrium; Acidosis, Lactic; Aged, 80 and over; Comorbidity; Diabetes Mellitus, Type 2; Diuretics; Drug Monitoring; Female; Humans; Hypoglycemic Agents; Kidney Failure, Chronic; Lactates; Metformin; Polypharmacy; Renal Dialysis; Sodium Bicarbonate

Topics: Acidosis, Lactic; Angiography, Digital Subtraction; Blood Gas Analysis; Contrast Media; Diabetes Mellitus, Type 2; Fatal Outcome; Heart Arrest; Humans; Hypoglycemic Agents; Intubation, Intratracheal; Iohexol; Male; Metformin; Middle Aged; Postoperative Complications; Radiographic Image Enhancement; Renal Insufficiency; Respiration, Artificial; Respiratory Distress Syndrome; Sodium Bicarbonate; Subarachnoid Hemorrhage; Tomography, X-Ray Computed

Metformin, an antihyperglycemic, is widely used in the treatment of type 2 diabetes mellitus (DM). A rare, but important complication associated with this drug is the development of lactic acidosis: Overall mortality of lactic acidosis is approximately 50%. Certain subsets of patients taking metformin are at greater risk of developing lactic acidosis. This report discusses the development of metformin-associated lactic acidosis in four older adults admitted to an institution during a 2-month period, treatments, and outcomes. We recommend an aggressive treatment strategy of hemodialysis followed by peritoneal dialysis, continuous bicarbonate infusion, and tight glucose control. We review the cautions and contraindications of metformin use for the treatment of type 2 DM and report an educational plan for residents and staff instituted to improve drug complication awareness and reduce mortality.

Topics: Acidosis, Lactic; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hydrogen-Ion Concentration; Hypoglycemic Agents; Infusions, Intravenous; Male; Metformin; Risk Factors; Sodium Bicarbonate

Topics: Acidosis, Lactic; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Male; Metformin; Sodium Bicarbonate

The reliability of urine glucose testing to monitor diabetic control was investigated in patients attending the Diabetic Clinic of the Tikur Anbassa Hospital in Addis Ababa between October 1994 and January 1995 with the aim of utilising it for those with a normal renal threshold who cannot afford the cost of home blood glucose monitoring. Clinically important fasting blood glucose values were taken as those > 180 mg/dl and important urine glucose values as those > or = 0.25% by Clinitest. Capillary blood glucose was determined by visual and metre readings. Urine was tested for glucose by the standard Clinitest method. There were 265 patients, 126 IDDM and 139 NIDDM. Urine glucose corresponded satisfactorily with FBG in 80% of the patients. The sensitivity, specificity, positive and negative predictive values of urine glucose results by Clinitest in comparison with FBG by metre determination were 71%, 90%, 90% and 70% and by visual determination 71%, 86%, 80%, 79% respectively. On the basis of these results we conclude that urine glucose testing by Clinitest provides reliable information in more than 70% of our diabetic patients the majority of whom cannot afford the cost of home blood glucose monitoring.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Citric Acid; Copper Sulfate; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycosuria; Humans; Indicators and Reagents; Male; Reproducibility of Results; Sensitivity and Specificity; Sodium Bicarbonate

Topics: Acidosis; Aged; Bicarbonates; Diabetes Mellitus, Type 2; Humans; Lactates; Male; Metformin; Middle Aged; Renal Dialysis; Sodium Bicarbonate

The effects of incorporating Fybogel (3.5 and 7 g doses), Metamucil (7 g) or guar gum (2.5 and 14.5 g doses) in a drink containing 50 g glucose on plasma glucose, plasma insulin and gastric emptying were studied in thirty-eight normal volunteers. In addition, the effects of Fybogel (7 g) on glucose tolerance, plasma insulin and gastric emptying were measured in fourteen non-insulin-dependent diabetics. Both doses of guar gum significantly lowered plasma glucose and plasma insulin responses to the oral glucose load in normal subjects, although 14.5 g guar gum did not delay the half-time for gastric emptying. Neither Fybogel nor Metamucil had significant effects on plasma glucose responses in normal subjects. In addition, Fybogel (at either dose) had no significant effects on plasma insulin levels, or on gastric emptying in normal subjects or on plasma glucose and insulin responses in diabetic patients. The viscosity of ispaghula solutions ( Fybogel ) was lower than that of guar gum solutions.

Topics: Adult; Aged; Bicarbonates; Blood Glucose; Citrates; Citric Acid; Diabetes Mellitus, Type 2; Dietary Fiber; Drug Combinations; Female; Galactans; Gastric Emptying; Glucose; Glucose Tolerance Test; Humans; Insulin; Male; Mannans; Middle Aged; Plant Extracts; Plant Gums; Psyllium; Sodium Bicarbonate

Topics: Accidents, Home; Adult; Aged; Child, Preschool; Citrates; Citric Acid; Copper Sulfate; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Male; Middle Aged; Sodium Bicarbonate