Severe hypernatremia in hyperglycemic conditions;managing it effectively:A case report

BACKGROUND Diabetic ketoacidosis(DKA)and hyperglycemic hyperosmolar state(HHS)are common acute complications of diabetes mellitus with a high risk of mortality.When combined with hypernatremia,the complications can be even worse.Hypernatremia is a rarely associated with DKA and HHS as both are usually accompanied by normal sodium or hyponatremia.As a result,a structured and systematic treatment approach is critical.We discuss the therapeutic approach and implications of this uncommon presentation.CASE SUMMARY A 62-year-old man with no known past medical history presented to emergency department with altered mental status.Initial work up in emergency room showed severe hyperglycemia with a glucose level of 1093 mg/dL and severe hypernatremia with a serum sodium level of 169 mEq/L.He was admitted to the intensive care unit(ICU)and was started on insulin drip as per DKA protocol.Within 12 h of ICU admission,blood sugar was 300 mg/dL.But his mental status didn’t show much improvement.He was dehydrated and had a corrected serum sodium level of>190 mEq/L.As a result,dextrose 5%in water and ringer's lactate were started.He was also given free water via an nasogastric(NG)tube and IV Desmopressin to improve his free water deficit,which improved his serum sodium to 140 mEq/L.CONCLUSION The combination of DKA,HHS and hypernatremia is rare and extremely challenging to manage,but the most challenging part of this condition is selecting the correct type of fluids to treat these conditions.Our case illustrates that desmopressin and free water administration via the NG route can be helpful in this situation.

Antihyperglycemic effects of the methanol leaf extract of Diaphananthe bidens in normoglycemic and streptozotocin—induced hyperglycemic rats

Objective:To evaluate the methanol leaf extract of Diaphonathe bidem(D.bidenx)(AFZEL EX SW) SCHLTR for antihyperglycemic activity in order to confirm it antidiabetic potential.Methods: D.bidenx was extracted by cold maceration for 48 h and concentrated in vacuo to yield D.bidenx extract(DBE).Hyperglycemia was induced by intraperitoneal administration of slreplozotocin (75 mg/kg).Oral glucose tolerance test was done with 2 g/kg glucose load in normal rats.DBE (150.300 and 600 mg/kg) was administered orally,while tolbutamide(100 mg/kg.p.o.) was used as the standard reference drug.Blood glucose levels determined using ACCUCHEK glucose autoanalyzer. The acute toxicity and phytochemical studies were also carried out.Results:DBF. (600 mg/kg) and tolbutamide(100 mg/kg) significantly(P【0.05,0.005) reduced blood glucose levels of rats between 120 and 480 nun post administration in normal rats.In the streptozotoeininduced hyperglycemic rats,DBE(150.300.600 mg/kg) caused significant(P【0.001)dose- and time- dependent reduction in the blood glucose levels by 1.7%.22.8%and 43.4%,respectively at 480 min compared to the negative control group.DBE(600 mg/kg) reduced the blood glucose level of rats by 1.2%in the oral glucose tolerance test when compared with the normal saline treated group.The acute toxicity test showed that DBE was safe at the doses used and the phytochemical screening revealed the presence of saponins,steroids,tannins and terpernoids.Conclusions:D. bidens extract possess antihyperglycemic activity which may be mediated through pancreatic and extra-pancreatic pathways,thereby justifying it folkloric use.

The effects of consumption of raw garlic on serum lipid level, blood sugar and a number of effective hormones on lipid and sugar metabolism in hyperglycemic and/or hyperlipidemic individuals ——Benefit of raw garlic consumption

Diabetes mellitus is one of the worldwide largest growing metabolic diseases. In this study the effects of consumption of raw garlic on serum lipid level, blood sugar and a number of effective hormones on lipid and sugar metabolism (thyroid hormones and insulin) in individuals either with high level of blood sugar or lipid were investigated. Eighty five volunteers having following clinical history enrolled in the study: Group 1: having blood sugar more than 126 mg/dl (30 vo-lunteers);Group 2: having cholesterol higher than 245 mg/dl (30 volunteers);Group 3: having blood sugar over 126 mg/dl and cholesterol more than 245 mg/dl (25 volunteers). In group 1, there wasn’t a sig-nificant differences between biochemical factors be-fore and after garlic consumption, whereas, in the second group after 6 weeks of garlic consumption a decline in cholesterol (P < 0.001), FBS and TG (P < 0.01) was observed but HDL-C (P < 0.001) was in-creased. Six weeks after termination of garlic con-sumption, cholesterol (P < 0.001), FBS and TG (P < 0.05) were in- creased and HDL-C (P < 0.01) was de-creased. In the third group, total cholesterol (P < 0.001), FBS (P < 0.01) and HbA1c decreased while HDL-C was in- creased. Other factors, including thy-roid hormones (T3, T4), TSH and insulin showed no significant alte- ration. In conclusion our results shown that raw garlic consumption can reduce the FBS and Lipid in hyperglycemic and/or hyperlipidemic individuals.

The Formamidine Amitraz as a Hyperglycemic α-Agonist in Worker Honeybees(Apis mellifera mellifera L.)in Vivo

Intra-abdominal injection of amitraz(0.25 nmol per honeybee,i.e.,approx 2.3 nmol/g)to emerging worker bees,in vivo,led to a significant hypertrehalosemia(300-400%)followed by a hyperglucosemia(≈600%).Maxima were reached at 0.5 and 2h,respectively.A strong negative correlation between glucosemia and trehalosemia appeared after injection of pure phentolamine (1 nmol per bee),suggesting stimulation of trehalase activities.Simultaneous administration of the α-blocker at≥0.25 nmol per individual suppressed the hyperglycemic response of amitraz. The formamidine pesticide thus likely acts on the honeybee α-aminergic system.1989 Academic Press,Inc.

COVID-19 Vaccine Related Hyperosmolar Hyperglycemic State and Normalized Glycemia within 2 Months

To protect from COVID-19 pandemic, several vaccines were developed infection with expected immunity against a SARS-CoV-2 infection. Short time side effects are reported. New onset diabetes was reported after SARS-CoV-2 infection. Here we report a case of new onset diabetes presenting with hyperosmolar hyperglycemic state, whose symptoms followed right after the second dose of Pfizer-BioNTech COVID-19 Vaccine. He is a 56-year old, obese Afro-American Veteran with no family history of diabetes and with HbA1C of 5.6 forty-five days prior to the hospitalization. He noted polyurea and excessive thirst following the second dose Pfizer-BioNTech COVID-19 vaccine. Hospitalized with hyperosmolar state and HbA1C of more than 14, he was treated initially with insulin drip and changed to basal, bolus regimen. In addition, he had new onset of oral thrush, requiring antifungal therapy. He needed higher doses of insulin during hospitalization and at discharge. He rapidly recovered and could be tapered off insulin in 4 months and recovered to normal glycemic state. We conclude that this is the second state to present with hyperosmolar state, and first case with rapid recovery of glycemic state.

Effect of acupuncture treatment on nonketotic hyperglycemic hemichorea-hemiballismus:a case report

Nonketotic hyperglycemic hemichorea-hemiballismus is a rare syndrome in the clinic,and treatment is often delayed.Hypoglycemic therapy is the most widely used and effective treatment,but some patients experience a slower improvement.Other symptomatic treatment medicines have some degree of side effects.Acupuncture treatment is beneficial for hemichoreahemiballismus.A male patient,aged 59 years,first visited our hospital outpatient department due to motor agitation with involuntary movements of the right limb.He had a history of type 2 diabetes mellitus and poor blood glucose control.His serum glucose was 26.5 mmol/L(normal:4.4-6.1 mmol/L),and magnetic resonance imaging demonstrated an irregular area of high signal intensity in T1-weighted imaging,low signal intensity on T2-weighted imaging,and high signal intensity in the left corpus striatum in T2-FLAIR imaging.Hospitalization was recommended for the patient.After ruling out other possibilities,he was eventually diagnosed with nonketotic hyperglycemic hemichorea-hemiballismus.Intensive glycemic control was immediately started with subcutaneous injection and acupuncture treatment at“governor vessel 13 acupoints”,and the involuntary movements completely disappeared on the ninth day of hospitalization.The pathophysiology of nonketotic hyperglycemic hemichorea-hemiballismus is unclear.Different patient histories lead to different brain tissue conditions,and relapses and uncontrolled blood glucose add difficulties to treatment.According to Traditional Chinese Medicine theory,insufficient kidney essence leads to brain dystrophy and causes the symptoms of hemichorea-hemiballismus.Research evidence has shown that acupuncture at"governor vessel 13 acupoints"has a beneficial treatment effect on nonketotic hyperglycemic hemichorea-hemiballismus.

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4

BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.

Hyperglycemic memory in diabetic cardiomyopathy

Cardiovascular diseases account for approximately 80%of deaths among individuals with diabetes mellitus,with diabetic cardiomyopathy as the major diabetic cardiovascular complication.Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy,fibrosis,apoptosis,and other pathophysiological changes.Although glycemic control has long been at the center of diabetes therapy,multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes.This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level.This process is now referred to as hyperglycemic memory(HGM)phenomenon.We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.

Construction of Saccharomyces cerevisiae Strain Stably Expressing a Fusion Protein Containing Ten Tandem Recombinant Human Glucagon-like Peptide-1 Analogues

The recombinant Saccharomyces cerevisiae strain stably expressing recombinant human glucagon-like peptide-l（rhGLP-1） analogue, as a potential oral drug delivery system for diabetes type II treatment, was successfully constructed by the homologous recombination between chromosomal DNA and yeast and integrating vector pNK-GLP containing yeast ribosomal DNA fragments. The amount of rhGLP-I analogue fusion protein in transformant SG2 reached ca. 0.84 mg per gram of packed cells when SG2 was grown for 24 h in the YPD medium with a inoculum and medium ratio of 1：1. Oral administration of 5 g lyophilized SG2/kg to hyperglycemic rats decreased serum glucose from （24.8±1.40） to （21.2±1.36） mmol/L.

Influence of gastric inhibitory polypeptide on pentagastrinstimulated gastric acid secretion in patients with type 2 diabetes and healthy controls

AIM： Gastric inhibitory polypeptide is secreted from intestinal K-cells in response to nutrient ingestion and acts as an incretin hormone in human physiology. While animal experiments suggested a role for GIP as an inhibitor of gastric secretion, the GIP effects on gastric acid output in humans are still controversial. METHODS： Pentagastrin was administered at an infusion rate of 1 μg . kg^-1 . h^-1 over 300 min in 8 patients with type 2 diabetes （2 female, 6 male, 54± 10 years, BMI 30.5 ± 2.2 kg/m^2; no history of autonomic neuropathy） and 8 healthy subjects （2/6, 46 ± 6 years., 28.9 ± 5.3 kg/ m^2）. A hyperglycaemic clamp （140 mg/dl） was performed over 240 min. Placebo, GIP at a physiological dose （1 pmol . kg^-1 . min^-1）, and GIP at a pharmacological dose （4 mol . kg^-1 . min^-1） were administered over 60 min each. Boluses of placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at the beginning of each infusion period, respectively. Gastric volume, acid and chloride output were analysed in 15-min intervals. Capillary and venous blood samples were drawn for the determination of glucose and total GIP. Statistics were carried out by repeated-measures ANOVA and one-way ANOVA. RESULTS： Plasma glucose concentrations during the hyperglycaemic clamp experiments were not different between patients with type 2 diabetes and controls. Steady-state GIP plasma levels were 61 ±8 and 79 ± 12 pmol/I during the low-dose and 327±35 and 327± 17 pmol/I during the high-dose infusion of GIP, in healthy control subjects and in patients with type 2 diabetes, respectively （P= 0.23 and p 0.99）. Pentagastrin markedly increased gastric acid and chloride secretion （P〈 0.001）. There were no significant differences in the rates of gastric acid or chloride output between the experimental periods with placebo or any dose of GIP. The temporal patterns of gastric acid and chloride secretion were similar in patients with type 2 diabetes and healthy controls （P= 0.86 and P= 0.61, respectively）. CONCLUSION： Pentagastrin-stimulated gastric acid secretion is similar in patients with type 2 diabetes and healthy controls. GIP administration does not influence gastric acid secretion at physiological or pharmacological plasma levels. Therefore, GIP appears to act as an incretin rather than as an enterogastrone in human physiology.

Hyperglycemia Induced Apoptosis Changes in Salivary Gland Cells of Mice

If the function of salivary glands that secrete saliva is degraded, saliva secretion will decrease and symptoms of xerostomia will appear. Although symptoms of xerostomia are often felt by patients with diabetes, the relationship between diabetes and xerostomia is currently unclear. In relation to DM, there are studies on salivation flow and saliva composition, but there are not studies of apoptosis of salivary gland cells. The objective of this study was to investigate whether apoptosis in salivary glands of mice with hyperglycemic, a symptom of diabetes, might be altered based on immunohistochemical analysis. This study used mice with hyperglycemia. Immunohistochemistry and Western blot analyses were performed using Fas, Bax, and cleaved caspase-3 antibodies. These antibodies are used not only as death receptors, but also are antibodies that activate upstream and downstream signals of apoptosis. TUNEL assay was performed to detect apoptosis by immunofluorescence using TdT enzyme. It was observed that the expression level of apoptosis signaling molecules and TUNEL positive cells were increased in hyperglycemia group (HG). As a result, there are many apoptosis cells in the HG groups of the salivary gland. The results of this study, the function of salivary gland could occur deteriorated due to apoptosis on salivary gland cells by hyperglycemic, a characteristic of diabetes.

The Impact of the FreeStyle LibreTM Flash Glucose Monitoring System on Glycemic Control in Patients with Diabetes;Observational Multicenter 15-Months Study

Objectives: The study was to determine the impact of using the FreeStyle LibreTM flash glucose monitoring system on glycemic control and the rate of events due to diabetes in people with diabetes from different types and age groups. Methods: a retrospective cohort chart review study was carried out at three centers in the Taif region in the Kingdom of Saudi Arabia: The study was approved by an accredited centralized institutional review board. Paper or electronic medical records were included for individuals of any age with diabetes (type 1, type 2, gestational diabetes) managed with diet, insulin therapy, or/and oral antihyperglycemic medication and/or non-insulin injection therapy. The primary outcome measure was the laboratory HbA1c level as well as reduction. Secondary outcome measures were frequency of severe hypoglycemia, admission to hospital or ER visit related to diabetes complications, and severe hyperglycemia (DKA or HHS). Results: Data was analyzed from 1695 patients. The average HbA1c before using the flash glucose monitoring system was 9.60% ± 1.44% and 3 months HbA1c after using the FreeStyle LibreTM flash glucose monitoring system was 8.70% + 1.45% for a difference of -0.90% ([95% CI -0.92: -0.88];p 65 years, (p-values Conclusion: The benefits of using the FreeStyle LibreTM flash glucose monitoring system are self-evident in reducing HbA1c and events due to hyperglycemia or hypoglycemia.

Heavy metal stress induced hyperglycemia in blue swimmer crab, Portunus pelagicus

The study was to find out the effect of cadmium and mercury on levels of hemolymph glucose, crustacean hyperglycemic hormone（CHH） and hepatopancreas glycogen in the blue swimmer crab Portunus pelagicus. The experiments were performed in both intact and eyestalk ablated crabs. Quantification of CHH was done by the indirect ELISA with the aid of primary anti-Carcinus maenas-CHH antibody. Higher glucose concentration was observed on exposure to 8×10^–6 of cadmium（（825.6±5.42） μg/m L） and 6×10^–6 of mercury（（90.5±6.25） μg/m L）after 48 h and 24 h respectively. Higher level of hemolymph glucose was observed in eyestalk intact crabs on exposure to cadmium and mercury than eyestalk ablated crabs. Decrease in the levels of CHH was observed in both eyestalk intact and ablated crabs on heavy metal exposure. Decline of the hepatopancreas glycogen level was also witnessed with the exposure to heavy metal, which validated its utilization in the production of glucose. Thus this study brings to light, the variations in hemolymph glucose, CHH and hepatopancreas glycogen on heavy metal stress. These carbohydrate metabolites can be used as biomarkers in assessing heavy metal contamination in water bodies.