Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort. METHODS: We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons. RESULTS: The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m-2). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (- 4.9%, P = 0.02), small LDL-P (- 20.8%, P = 1.2 × 10-12), LDL-P size (+ 1.1%, P = 6.0 × 10-10), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10-16), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 × 10-7), triglyceride/HDL-C ratio (- 29.1%, P < 10-16), large VLDL-P (- 38.9%, P = 4.2 × 10-15), and LDL-C (+ 9.9%, P = 4.9 × 10-5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10-7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 × 10-5). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10-5). The UC group of 87 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m-2] showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C. CONCLUSIONS: A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after 1 year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased. Trial registration Clinicaltrials.gov: NCT02519309. Registered 10 August 2015.

Distinct clinical characteristics and therapeutic modalities for diabetic ketoacidosis in type 1 and type 2 diabetes mellitus.

AIMS: Patients with type 1 diabetes often develop diabetic ketoacidosis (DKA). Reportedly, DKA in type 2 diabetes has higher mortality despite its limited occurrence. The exact clinical characteristics and therapeutic modalities yielding successful outcomes in DKA type 2 diabetes remain unknown. METHODS: This retrospective study compared the clinical features and detailed treatment of consecutive type 1 and type 2 diabetes patients hospitalized with DKA between January 2001 and December 2014. RESULTS: We report on 127 patients with type 1 and 74 patients with type 2 diabetes whose DKA was successfully treated. The most frequent precipitating cause for DKA was infectious disease for patients with type 1 diabetes and consumption of sugar-containing beverages for those with type 2 diabetes. Type 2 diabetes patients showed higher mean plasma glucose levels than those with type 1 diabetes (48.4±21.6, vs. 37.1±16.4mmol/l, P<0.01) and higher serum creatinine, blood urea nitrogen, and hemoglobin levels, which normalized after DKA resolution. Compared with type 1 diabetes patients, those with type 2 diabetes required distinctly higher daily total insulin dosage (35.9±37.0U, vs. 20.2±23.3U, P<0.01), larger replacement fluid volumes (4.17±2.69L, vs. 2.29±1.57L, P<0.01) and greater potassium supplementation (23.9±36.5mEq, vs. 11.2±17.9mEq, P<0.01) to resolve DKA and reduce plasma glucose level to ≤16.7mmol/l. CONCLUSIONS: DKA patients with type 2 diabetes required management with a modified treatment protocol to resolve their profound hyperglycemia and dehydration compared with those with type 1 diabetes.

Fluid and Electrolyte Therapy in Diabetic Ketoacidosis.

Diabetic ketoacidosis is a dynamic disease that requires regular reassessment of an affected patient. Typical treatment regimens include crystalloid fluid therapy, insulin, and supplementation of dextrose, phosphorus, and potassium. This article presents an approach to and considerations for treatment of a diabetic ketoacidotic dog or cat.

Looking at diabetic ketoacidosis through electrocardiogram window!

BACKGROUND: Initial serum potassium (K+) in diabetic ketoacidosis (DKA) often does not reflect the true amount of total body K+ storage, and it is not a good predictor of subsequent hypokalemia. In this study, we tested the hypothesis that a deficiency of the total body K+ storage can be detected initially on surface electrocardiography (ECG). METHOD: Medical records of 350 patients with a diagnosis of DKA were reviewed. Data regarding serial basic metabolic panels, arterial blood gases, serum ketones, and total K+ replacement that patient received during admission were collected. We compared biochemical findings for patients with and without QTU corrected (QTUc) prolongation by using the t test. Patients who were taking medications known to affect QTUc or cause ST-T changes were excluded. RESULTS: After exclusion criteria, 61 patients were enrolled in this study. In 38 patients (62.9%), QTUc was more than or equal to 450 milliseconds. Patients with prolonged QTc received statistically more K+ supplementation during admission (P = .014). They also had lower serum K+ level during their hospital course (P = .002) compared to patients with normal QTUc intervals. No significant difference was found between initial serum K+, calcium, glucose, anion gap, acidosis, age, or heart rate between these 2 groups. CONCLUSION: The significant relationship between K+ depletion and the ECG changes observed in this study deserves further consideration. Our findings confirm the concept that the ECG is an easy and reliable tool for early diagnosis of hypokalemia in patients with DKA.

Acid-base disorder analysis during diabetic ketoacidosis using the Stewart approach--a case report.

This case report presents a 49 year-old female with type 1 diabetes admitted to the intensive care unit with acute respiratory failure and severe diabetic ketoacidosis with an initial measurement of blood glucose level of 1,200 mg L⁻¹, pH 6.78, serum HCO3 ⁻ 3.2 mmoL L⁻¹ and BE -31.2 mmoL L⁻¹. Analysis of the blood gasometric parameters with the Stewart approach and the traditional Henderson-Hasselbalch concept enabled the discovery of metabolic acidosis caused by unidentified anions (mainly ketons). A treatment protocol with intensive fluid management with 0.9% NaCl, intensive intravenous insulin therapy, and potassium supplementation was administered. Analysis of the gasometric parameters after 12 hours of treatment according to the Stewart approach compared to the Henderson-Hasselbalch concept disclosed that metabolic acidosis caused by the unidentified anions has resolved almost completely and been replaced by metabolic hyperchloremic acidosis. The hyperchloremic acidosis was caused by the intensive fluid resuscitation with 0.9% NaCl, which contains a high chloride load, exceeding the chloride levels observed in human serum. Fluid management with balanced fluids other than saline was continued, together with intravenous insulin infusion, potassium supplementation, and 5% glucose administration. Analysis of this case study revealed the advantages of the Stewart approach to acid base abnormalities compared to the traditional Henderson-Hasselbalch concept. The Stewart approach allows the diagnosis of the exact causes of severe life-threatening metabolic acidosis and the appropriate modification of the therapeutic mangement of patients with diabetic ketoacidosis.

Occult infarct with acute hemorrhagic stroke in juvenile diabetic ketoacidosis.

Diabetes ketoacidosis (DKA) is one of the common complications of type I insulin-dependent diabetes mellitus. Neurological deterioration during an episode of DKA is usually assumed to be caused by cerebral edema and cerebral vascular accidents. However, hemorrhagic stroke is a very rare complication of juvenile DKA. We describe a girl who had newly diagnosed insulin-dependent diabetes mellitus with juvenile DKA developed intracerebral hemorrhage.

Severe hypernatremia and hyperosmolality exacerbated by an herbal preparation in a patient with diabetic ketoacidosis.

This article reports a case of severe reversible hypernatremia exacerbated by an herbal agent "goldenseal" (Hydrastis canadensis) in an 11-year-old girl with new onset type I diabetes mellitus presented with diabetic ketoacidosis. A literature review is presented and possible mechanism of hypernatremia caused by this herbal preparation is discussed.

Pretreatment clinical and laboratory evaluation of cats with diabetes mellitus: 104 cases (1992-1994).

OBJECTIVE: To assess pretreatment clinical and laboratory findings in cats with diabetes mellitus and to determine the influence of ketoacidosis on pretreatment findings. DESIGN: Retrospective case series. ANIMALS: 104 cats with diabetes mellitus, 38 of which had ketoacidosis. PROCEDURE: Medical records of cats with diabetes mellitus examined over a 20-month period were reviewed. Cats that had received previous treatment for diabetes mellitus, or for which medical records were incomplete, were excluded from this study. RESULTS: Cats ranged in age from 1 to 19 years (median, 11 years). Male cats were twice as likely to develop diabetes as females. The most common historical signs were polyuria, polydipsia, weight loss, and diminished activity. Anorexia or poor appetite was reported more commonly than polyphagia, especially in cats with ketoacidosis. Diminished activity, anorexia, weakness, and vomiting were all significantly more common in ketoacidotic cats than in nonketoacidotic cats. Forty-four cats were considered thin, and 34 were considered obese. All cats had hyperglycemia and most had hypercholesterolemia and high activities of 1 or more hepatic enzymes. Compared with nonketoacidotic cats, ketoacidotic cats were more likely to have had low serum electrolyte values. All cats had glucosuria and 42 (40.4%) had ketonuria. Baseline serum insulin concentrations were measured in 18 cats and were low or at the low end of the reference range in 14 (77.8%) cats. Serum fructosamine concentration, determined in 22 cats, was high in 20 (90.9%) cats. Twenty-three of the 104 (22.1%) cats had concurrent disease, the most common of which were hyperthyroidism, inflammatory bowel disease, and eosinophilic granuloma complex. CLINICAL IMPLICATIONS: In more than a third of cats, diabetes mellitus is complicated by development of ketoacidosis, which increases the severity of clinical and laboratory abnormalities. Diagnosis of diabetes mellitus is made on the basis of signalment (e.g., middle-aged to old male cats), owner complaints (e.g., polyuria, polydipsia, and weight loss), physical examination findings (e.g., lethargy or muscle wasting), and laboratory findings (e.g., hyperglycemia and glucosuria).

[Critical study of diabetic ketoacidosis in children. Initial description and course during the first 24 hours of treatment]. / Etude critique de l'acidocétose diabétique de l'enfant. Description initiale et évolution au cours des 24 premières heures de traitement.

A critical analysis of the evolution during the first 24 hours was undertaken in 41 children and adolescents (age: 10.1 +/- 4.6 years) treated for diabetic ketoacidosis. Three of 4 children presented with ketoacidosis revealing diabetes. One of 4 was less than 6 years of age. Severe ketoacidosis (pH less than 7.15) concerned one third of children and were more frequent in the group of adolescents with already known diabetes. In these patients, ketoacidotic decompensation was attributed to psychosocial factors in most cases. Evolution was favorable in all cases, without complication. Blood glucose levels decreased from 28.7 mmol/l on arrival to 16.2 mmol/l after 2 hours of treatment and became stable at 10 mmol/l from the 12th to the 24th hours. The corrected blood sodium levels were stable, showing the adequacy of infusion solute osmolarities. Blood potassium was maintained at a normal level owing to early potassium supplementation. Ketoacidosis was corrected after about 12 hours, without bicarbonate administration when pH was greater than 7.15. Average perfused volumes were 3 l/m2/24 hours. Insulin doses were 2 UI/kg/24 hours and were inversely correlated with the admission pH (r = -0.6; p = 0.0001). This study shows the efficacy of a treatment taking into account the pathophysiology of diabetic ketoacidosis and the knowledge of the complication risk factors, by foreseeing the adjustments to be done with respect to individual and/or at risk situations. These precise descriptive data, collected on a large group of patients, establish a reference basis to follow evolution in the course of the treatment of diabetic ketoacidosis in children.

Mixed acid-base abnormalities in diabetes.

This study is a description of a patient who exhibited diabetic ketosis associated with an alkalosis rather than acidosis and a review of eight previously reported cases. Precipitating factors for this syndrome are severe vomiting with loss of hydrogen, potassium, and chloride ions, and dehydration. The ingestion of alkali may also result in this mixed acid-base disturbance. Treatment consists primarily of replacement of potassium and chloride. All reported patients had received large doses of insulin for initial therapy; however, limited insulin (20 U) therapy in this patient almost completely reversed the metabolic abnormality with 12 hours.

Diabetic ketoacidosis: new concepts and trends in pathogenesis and treatment.

New concepts concerning the pathogenesis and therapy of diabetic ketoacidosis are reviewed. The regulation of ketogenesis by intrahepatic enzymic processes and the roles of insulin deficiency or glucagon or other counterregulatory hormone excess are summarized. Major emphasis is placed on an analysis of the use of low-dose insulin regimens for the treatment of ketoacidosis. Most patients with diabetic ketoacidosis will respond to low-dose, hourly, intravenous or intramuscular regular insulin. Low doses of insulin are as effective as high doses and have fewer associated complications of hypoglycemia and hypokalemia. Phosphorus deficiency is common in diabetic ketoacidosis and hypophosphatemia usually becomes manifest within 4 to 12 h of institution of therapy. Phosphorus supplementation is now generally recommended to replete erythrocyte 2,3-diphosphoglycerate and improve oxygen delivery to tissues. Coexistent and biochemically significant lactic acidosis is a relatively infrequent complication of diabetic ketoacidosis and when present is usually due to underlying disorders associated with poor tissue perfusion.

Low-dose insulin in the treatment of diabetic ketoacidosis.

Severe diabetic ketoacidosis remains a lethal condition. Many deaths occur during therapy and are avoidable. Treatment includes rehydration, administration of insulin and potassium, and clinical care. For many years very large doses of insulin were used. Recently, it has been suggested that such large doses are unnecessary and lead to undue hypokalemia, hypoglycemia, and osmotic disequilibria. Many studies are now available that show that low doses of insulin given as continuous intravenous infusions (4 to 10 units/hr) or as hourly intramuscular injections (20 units initially, then 5 units/hr) are as effective as large doses in treating severe ketoacidosis. The new regimens are simple to use, predictable, and safe. Potassium shifts are less than with large insulin doses and insulin resistance has been shown to be a relatively minor problem. The new regimens are particularly suitable for use in nonspecialist centers.