Ketosis-prone diabetes mellitus:A phenotype that hospitalists need to understand

Diabetes has been classified mainly into types 1 and 2.Some type 2 diabetes patients,when developing ketosis,have been labeled as having atypical diabetes.Lately,syndromes of ketosis-prone diabetes,primarily in patients who we previously classified as type 2 diabetics,have emerged,and calls are being made to even reclassify diabetes.This mini-review will extensively deal with the historical,molecular,phenotypical,and clinical basis of why ketosis-prone diabetes is different than the traditional principles of type 1 and 2 diabetes and should be classified as such.Clinicians,especially those who are not diabetologists or endocrinologists,as well as hospitalists,intensivists,and primary care providers,will greatly benefit from this review.

Hepatic metabolomics and transcriptomics to study susceptibility to ketosis in response to prepartal nutritional management

Background:Ketosis in dairy cows is associated with body fat mobilization during the peripartal period.Sub-clinical and clinical ketosis arise more frequently in cows that are overfed energy during the entire dry(last 50 to 45 days prior to parturition)or close-up period(last^28 days prepartum).Methods:A retrospective analysis was performed on 12 cows from a larger cohort that were fed a higher-energy diet[1.54 Mcal/kg of dry matter(DM);35.9%of DM corn silage and 13%of DM ground corn]during the close-up dry period,of which 6 did not develop clinical ketosis(OVE,0.83 mmol/L plasma hydroxybutyrate;BHB)and 6 were diagnosed with clinical ketosis(KET,1.4 mmol/L BHB)during the first week postpartum.A whole-transcriptome bovine microarray(Agilent Technologies)and metabolomics(GC-MS,LC-MS;Metabolon~?Inc.)were used to perform transcript and metabolite profiling of liver tissue harvested at-10 days relative to parturition which allowed to establish potential associations between prepartal transcriptome/metabolome profiles and susceptibility to clinical ketosis postpartum.Results:Cows in KET had greater(P=0.01)overall body weight between-2 and 1 week around parturition,but similar body condition score than OVE.Although dry matter intake(DMI)did not differ prepartum,KET cows had lower(P<0.01)DMI and similar milk yield as OVE cows during the first week postpartum.Transcriptome analysis revealed a total of 3065 differentially expressed genes(DEG;P≤0.05)in KET.Metabolomics identified 15 out of 313 total biochemical compounds significantly affected(P≤0.10)in KET.Among those,greater concentrations(P≤0.06,+2.3-fold)of glycochenodeoxycholate in KET cows also have been detected in humans developing non-alcoholic fatty liver disease.Bioinformatics analysis using the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database and the DEG revealed that,among the top 20 most-impacted metabolic pathway categories in KET,65%were overall downregulated.Those included’Metabolism of cofactors and vitamins’,’Biosynthesis of other secondary metabolites’,’Lipid’,’Carbohydrate’,and’Glycan biosynthesis and metabolism’.The lower relative concentration of glucose-6-phosphate and marked downregulation of fructose-1,6-bisphosphatase 2 and pyruvate dehydrogenase kinase 4 support a strong impairment in gluconeogenesis in prepartal liver of cows developing KET postpartum.Among the top 20 most-impacted non-metabolic pathways,85%were downregulated.Pathways such as’mTOR signalling’and’Insulin signalling’were among those.’Ribosome’,’Nucleotide excision repair’,and’Adherens junctions’were the only upregulated pathways in cows with KET.Conclusions:The combined data analyses revealed more extensive alterations of the prepartal liver transcriptome than metabolome in cows overfed energy and developing ketosis postpartum.The causative link between these tissue-level adaptations and onset of clinical ketosis needs to be studied further.

Trends of Kalemia at Diagnosis of Acidosis versus Non-Acidosis Diabetic Ketosis Décompensations in Ouagadougou (Burkina Faso)

Introduction: Electrolyte’s profile in non-acidosis diabetic ketosis is poorly specified. We aimed to determine the nature of diabetic ketosis decompensations as well as the profile of kalemia and factors associated with its disorders at diagnosis of acidosis compared to non-acidosis diabetic ketosis. Methods: The study was retrospective from 1 January 2010 to 31 December 2011 in Yalgado Ouédraogo teaching hospital. Diabetic in-patients suffering from simple ketosis, keto-acidosis or mixed decompensation, who achieved blood electrolytes assessment before intensive insulin therapy were included. Results: Sixty two patients were studied. The sex ratio was 0.7 and the mean age was 41.7 years. Keto-acidosis, simple ketosis and mixed decompensation were diagnosed respectively in 18 (29%), 32 (51.6%) and 12 (19.4%) patients. Kalemia was normal in 42 (67.7%), while hypokalemia and hyperkalemia were reported respectively in 11 (17.8%) and 9 (14.5%) patients. Kalemia was often normal in all types of ketosis decompensation and disorders of kalemia occurred more in patients with keto-acidosis (50%) than those with simple ketosis (21.9%);p = 0.04. Renal failure was diagnosed in 10 patients (50%) with and 2 (4.8%) without kalemia’s disorders;p = 0.0001. Seven patients (35%) with and 4 (9.5%) without kalemia’s disorders suffered from unconsciousness;p = 0.02. It happens more in hyperkalemia (44.4%) than in normal kalemia condition (9.5%);p = 0.02. Conclusion: If kalemia is often normal in all types of diabetic ketosis emergencies, hypokalemia is the most initial frequent potassium disorder.

The effects of nutritional ketosis induced by Bigu-herbs regimen and ketogenic diet on diseases and aging

The Bigu-herbs regimen,a Taoism(Taoism is an ancient Chinese Taoist philosophy system)special health-preserving technique to achieve longevity through strict abstinence from food,limits the intake of grains and uses herbs to replace normal diet to gain energy.Practicing Bigu-herbs regimen for several weeks to several years can make one lose weight,prevent diseases,and prolong life.The modern ketogenic diet(KD)mainly limits carbohydrate intake and increase fat intake.The low-carbohydrate,high-fat,and adequate protein diet is well known for its antiepileptic and neurotrophic effects.Limiting the intake of carbohydrate results in energy metabolism reprogramming to mobilize the steatolysis,energize and promote ketone bodies(KBs)production,achieving a state of nutritional ketosis(NK).The researchers summarized how ketone bodies or NK affects diseases and the aging process,as well as the side effects of KD.NK has a favorable effect on caloric intake,lipid parameters,glycemic index,and insulin sensitivity;moreover,it can be used as a treatment option for diabetes,obesity,and other metabolic disorders.NK is recognized as being neuroprotective and is good for epilepsy,Alzheimer’s disease,and emotional disturbance.Targeting the metabolic differences between tumor and normal cells,NK limits the use of glucose and impairs energy metabolism in cancer cells,inhibiting their growth and rendering them susceptible to clinical treatments.NK also affects inflammation and the release of cytokines,regulate gut flora,extend longevity and health span,and preserve physiologic functions.The side effects of KDs are controllable under the guidance of a specially trained dietitian and medical team.

Combination of nutritional ketosis and hyperoxygenation therapy-promising ground for integrative cancer treatment: a systematic review

Though the cancer is a multifactorial disease,where various types of cancers exhibit varying mechanisms,pathways,genetic and cellular defects,the study of tumor micro-environment confirms that upregulated glycolysis and hypoxia are the part and parcel of almost every cancer subtypes.Therefore,targeting them with nutritional ketosis and hyper-oxygenation therapies could create an unfavourable environment for cancers to thrive.The aim of this review is to study the significance of these interventions in the integrative cancer treatment.Extensive search has been carried out through the online scientific database like PubMed and other medical journals with the search words,‘cancer metabolism’,‘tumor micro environment’,‘hypoxia and tumor’,‘ketosis and cancer treatment’,‘hyperbaric oxygen therapy and cancer’and‘ozone therapy and cancer’.All biomolecule studies,preclinical and clinical studies,received as search results are reviewed.In addition,a nutritional book,named‘Healing with Whole Foods:Asian Traditions and Modern Nutrition’by Paul Pitchford is also referred.These studies recommend the use of various therapeutic approaches like ketogenic diet,ketone supplementation,hyperbaric oxygen therapy and intravenous ozone therapy,individually or in combination with standard therapies,based on its antitumor effects,safety,tolerability,its ability to potentiate the radio and chemo therapy,while decreasing its side effects and its efficiency to improve the quality of life.Rewardingly,when combined,the synergistic action of nutritional ketosis and hyperoxygenation therapies elicited profound,supra additive anti-cancer effects.As per present studies,these therapies are safe to include in an Integrative cancer treatment,though large clinical trials are needed to systematize its clinical usage.

Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with BHBA.Results We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic AMP.Conclusions We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

Sirtuin 3 regulation:a target to alleviateβ-hydroxybutyric acid-induced mitochondrial dysfunction in bovine granulosa cells

Background During the transition period,the insufficient dry matter intake and a sharply increased in energy consumption to produce large quantities of milk,high yielding cows would enter a negative energy balance(NEB)that causes an increase in ketone bodies(KBs)and decrease in reproduction efficiency.The excess concentrations of circulating KBs,represented byβ-hydroxybutyric acid(BHBA),could lead to oxidative damage,which potentially cause injury to follicular granulosa cells(fGCs)and delayed follicular development.Sirtuin 3(Sirt3)regulates mitochondria reactive oxygen species(mitoROS)homeostasis in a beneficial manner;however,the molecular mechanisms underlying its involvement in the BHBA-induced injury of fGCs is poorly understood.The aim of this study was to explore the protection effects and underlying mechanisms of Sirt3 against BHBA overload-induced damage of fGCs.Results Our findings demonstrated that 2.4 mmol/L of BHBA stress increased the levels of mitoROS in bovine fGCs.Further investigations identified the subsequent mitochondrial dysfunction,including an increased abnormal rate of mitochondrial architecture,mitochondrial permeability transition pore(MPTP)opening,reductions in mitochondrial membrane potential(MMP)and Ca^(2+)release;these dysfunctions then triggered the caspase cascade reaction of apoptosis in fGCs.Notably,the overexpression of Sirt3 prior to treatment enhanced mitochondrial autophagy by increasing the expression levels of Beclin-1,thus preventing BHBA-induced mitochondrial oxidative stress and mitochondrial dysfunction in fGCs.Furthermore,our data suggested that the AMPK-mTOR-Beclin-1 pathway may be involved in the protective mechanism of Sirt3 against cellular injury triggered by BHBA stimulation.Conclusions These findings indicate that Sirt3 protects fGCs from BHBA-triggered injury by enhancing autophagy,attenuating oxidative stress and mitochondrial damage.This study provides new strategies to mitigate the fGCs injury caused by excessive BHBA stress in dairy cows with ketosis.

Preserving finger length in a patient with symmetric digital gangrene under local anesthesia:A case report

BACKGROUND Case reports of symmetric digital gangrene resulting from high-dose vasopressors use in patients with alcoholic ketoacidosis,leading to cardiac arrest,are rare.To date,no specific treatment method for autolysis or surgical amputation or guidelines for determining the level of amputation have been established.CASE SUMMARY In this case report,we describe a treatment method that effectively preserved the function of fingers by surgical treatment under local anesthesia with a minimum operative time,while also preserving finger length to the maximum possible extent.CONCLUSION Our approach may contribute to improved postoperative quality of life by preserving finger length.

“酮粉法”连续一年监测大群奶牛酮病试验简报

为探寻监测奶牛酮病的方法,试验用“酮粉法”快速检验酮病的效果,探讨安徽省奶牛酮病的发病规律,为防治本病提供科学依据,在一年时间内,连续对安徽合肥保健奶牛场和淮南奶牛一场、二场的泌乳母牛,进行了全面的,每月一次的监测。通过对近一万头次的监测发现,这几个场奶牛酮病的发病率在头年的十一月份到第二年的四月份发病率较高(平均为3.7%),其中二月份发病率最高(6.62%)。

Euglycemic diabetic ketoacidosis:A missed diagnosis

Euglycemic diabetic ketoacidosis(DKA)is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose(less than 11 mmol/L).The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units;it may delay diagnosis and treatment causing worse outcomes.Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus.With the addition of sodium/glucose cotransporter-2 inhibitors in diabetes mellitus management,euglycemic DKA incidence has increased.The other causes of euglycemic DKA include pregnancy,fasting,bariatric surgery,gastroparesis,insulin pump failure,cocaine intoxication,chronic liver disease and glycogen storage disease.The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit,milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio.Euglycemic DKA is a diagnosis of exclusion and should be considered in the differential diagnosis of a sick patient with a history of diabetes mellitus despite lower blood glucose or absent urine ketones.The diagnostic workup includes arterial blood gas for metabolic acidosis,serum ketones and exclusion of other causes of high anion gap metabolic acidosis.Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration,electrolytes deficit and insulin replacement.The dextrosecontaining fluids should accompany intravenous insulin to correct metabolic acidosis,ketonemia and to avoid hypoglycemia.

Use of sodium bicarbonate and blood gas monitoring in diabetic ketoacidosis: A review

Diabetic ketoacidosis(DKA) is a severe and toocommon complication of uncontrolled diabetes mellitus. Acidosis is one of the fundamental disruptions stemming from the disease process, the complications of which are potentially lethal. Hydration and insulin administration have been the cornerstones of DKA therapy; however, adjunctive treatments such as the use of sodium bicarbonate and protocols that include serial monitoring with blood gas analysis have been much more controversial. There is substantial literature available regarding the use of exogenous sodium bicarbonate in mild to moderately severe acidosis; the bulk of the data argue against significant benefit in important clinical outcomes and suggest possible adverse effects with the use of bicarbonate. However, there is scant data to support or refute the role of bicarbonate therapy in very severe acidosis. Arterial blood gas(ABG) assessment is an element of some treatment protocols, including society guidelines, for DKA. We review the evidence supporting these recommendations. In addition, we review the data supporting some less cumbersome tests, including venous blood gas assessment and routine chemistries. It remains unclear that measurement of blood gas pH, via arterial or venous sampling, impacts management of the patient substantially enough to warrant the testing, especially if sodium bicarbonate administration is not being considered. There are special circumstances when serial ABG monitoring and/or sodium bicarbonate infusion are necessary, which we also review. Additional studies are needed to determine the utility of these interventions in patients with severe DKA and pH less than 7.0.

Early vs late oral nutrition in patients with diabetic ketoacidosis admitted to a medical intensive care unit

BACKGROUND Diabetic ketoacidosis(DKA) has an associated mortality of 1% to 5%. Upon admission, patients require insulin infusion and close monitoring of electrolyte and blood sugar levels with subsequent transitioning to subcutaneous insulin and oral nutrition. No recommendations exist regarding the appropriate timing for initiation of oral nutrition.AIM To assess short-term outcomes of oral nutrition initiated within 24 h of patients being admitted to a medical intensive care unit(MICU) for DKA.METHODS A retrospective observational cohort study was conducted at a single academic medical center. The patient population consisted of adults admitted to the MICU with the diagnosis of DKA. Baseline characteristics and outcomes were compared between patients receiving oral nutrition within(early nutrition group) and after(late nutrition group) the first 24 h of admission. The primary outcome was 28-d mortality. Secondary outcomes included 90-d mortality, MICU and hospital lengths of stay(LOS), and time to resolution of DKA.RESULTS There were 128 unique admissions to the MICU for DKA with 67 patientsreceiving early nutrition and 61 receiving late nutrition. The APACHE(Acute Physiology and Chronic Health Evaluation) IV mortality and LOS scores and DKA severity were similar between the groups. No difference in 28-or 90-d mortality was found. Early nutrition was associated with decreased hospital and MICU LOS but not with prolonged DKA resolution, anion gap closure, or greater rate of DKA complications.CONCLUSION In patients with DKA, early nutrition was associated with a shorter MICU and hospital LOS without increasing the rate of DKA complications.

The Effect of Ketogenic-Diet on Health

In recent years, the ketogenic diet is the most popular diet around the world. Therefore, keto diet, short for ketogenic, involves eating a high amount of fat, a moderate amount of protein and very few carbs. This research paper aims to know about the effect of a ketogenic diet on our body, to know about the mechanism of the ketogenic diet in treating neurodegenerative disorders and to know about the mechanism of the ketogenic diet in reducing the weight of our body. Also, the objective was to investigate the ketogenic diet stimulates ketogenesis which treats certain neurodegenerative disorders. Although this is high fats containing food it is beneficial for our body in certain conditions. It is also useful in the conditions in which the brain requires a low level of glucose so the brain starts utilizing ketone bodies. As the intake of carbohydrates is lowered so it is also used to reduce the weight of the body. In this research, the qualitative methodology has been adopted which refers to secondary sources of data. In this project, I used a variety of research that has also been undertaken by numerous researchers including dietitians who tend to support the positive benefits of using ketogenic diets to manage losing weight as well as other health problems that could result from overweight. Also, we used a table to show the difference between studies. Finally, it is important to note that the ketogenic-diet has created debate, partially although traditional dietary education has, for years, illustrated the adverse effects of high overall including trans-fat intake.

Study of the Management of Diabetic Metabolic Emergency in the National Teaching Hospital HKM of Cotonou

Objective: To study the epidemiological, clinical and therapeutic profile of diabetic metabolic emergencies. Patients and methods: This was a prospective study in descriptive and analytical referred conducted over a period of 6 months in the National Teaching Hosptial HKM of Cotonou December 1, 2011 to May 31, 2012. The patients included in the case of our study were those who, conscious or comatose, had submitted a diabetic hypoglycemia or abnormal blood sugar (2.5 g/l), with a positive glycosuria and ketonuria positive or not. All patients gave their consent for this study. Results: 2786 patients were admitted to the emergency room, 57 (2%) of acute metabolic decompensation of diabetes. DKA accounted for 1.1%, hyperosmolar hyperglycemic syndrome 0.5% and 0.4% hypoglycemia. For hyperglycemic decompensation, sex ratio was 0.8 for females with a mean age of 50.7 ± 16.9 (16-84). For hypoglycemia, male gender was predominant. As decompensation factors for hyperglycemia, infection was found in 54% (n = 30) of cases and stroke by 29% hypertension (n = 15). As for hypoglycemia triggers were dominated by dietary error (50%) and therapeutic errors (25%). 63% (n = 36) of patients underwent resuscitation. More than 3 out of 4 patients were resuscitated to insulin. 98% of patients were rehydrated. The outcome was favorable in 56% of cases. The death rate was 25 % (n = 14). Conclusion: Diabetes mellitus is a serious condition and its severity is mainly due to complications which can be acute or chronic.