Fasting Plasma Lactate Research Articles

EFFECTS OF PETROL CONTAMINATED DIET AND WATER ONGLUCOSE, LIVER GLYCOGEN, PLASMA LACTATE AND LIPID PROFILE IN MALE WISTAR RATS

Exposure to petrol have been shown to cause detrimental health effects. Literature is sparse on whether exposure to petrol causes metabolic disorders. This study investigated the effects of petrol contaminated diet andwater on blood glucose, liver glycogen, plasma lactate, triglycerides and lipid profile in male Wistar rats. The study was divided into two phases. Phase one study consisted of 15 male Wistar rats divided into three groups (n = 5/group). Groups 1-3 were given distilled water, petrol-contaminated diet (20 mL petrol/200 g rodent chow PCD), and petrol-contaminated water (0.5 mL/kg PCW) orally and respectively for .two weeks. In the phase two study, 15 male Wistar rats were divided into three groups (n = 5/group), animals in groups 1-3 received distilled water, petrol contaminated diet, and petrol-contaminated water orally and respectively for four weeks.At the end of the experiment, fasting blood glucose, liver glycogen, plasma lactate, triglycerides and lipid profie were measured.The results of this study showed that the administration of petrol contaminated diet and water caused significant increase in plasma lactate levels, triglycerides (TG),total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL)and a significant reduction in liver glycogen and high density lipoprotein( HDL) in male Wistar rats. In conclusion, the study revealed that, exposure of rats to petrol contaminated diet and water caused changes in lipid profile, altered glucose and lipid metabolism in male Wistar rats. Exposure to petrol should therefore be restricted or avoided.

227-LB: Elevated Plasma Lactate and the Risk for Metabolic Syndrome—Is Skeletal Muscle a Producer or Consumer?

Background: The incidence of metabolic diseases is rising and there is a dire need for early detection to implement prevention. Fasting plasma lactate concentrations have been shown to be elevated in individuals with obesity and predictive of type 2 diabetes. An elevated fasting lactate concentration could possibly be the product of a reduction in muscle oxidative capacity and increased muscle lactate output. However, it is unknown how early this is evident, as are the mechanisms involved. Aim: The aim of this study was to determine if fasting lactate concentrations were linked with a reduction in skeletal muscle oxidative capacity in a cohort without metabolic disease. Methods: Young (age 28 ± 7; N=21) overweight (BMI (27.1 ± 0.4 kg/m2) men (n=12) and women (n=9) were recruited for this study. Blood biomarkers were measured in the fasted state and body composition was determined by DXA. Muscle oxidative capacity was measured in skeletal muscle homogenates (vastus lateralis biopsy) using 14C-labeled labeled palmitate and pyruvate. Muscle lactate output was determined by microdialysis during a hyperinsulinemic euglycemic clamp procedure. Results: Elevated lactate was associated with elevated visceral adiposity (R2=.40, p=.003) , elevated triglycerides (R2=.56, p=.0001) , as well as elevations in systolic blood pressure (R2=.39, p=.003) . Subjects with higher lactate had lower ratio of fatty acid oxidation to pyruvate oxidation (ratio R2=.49, p=.002) . Muscle lactate uptake in the basal state of the clamp positively associated with plasma lactate (R2=.92, p=<.0001) ; however, in the insulin phase net lactate output was near zero. Conclusion: Individuals who are overweight but otherwise healthy have elevated plasma lactate that associates with parameters of the metabolic syndrome. Lactate was associated with a shift from lipid to carbohydrate oxidation. Muscle is a consumer of lactate in the fasted state, whereas adipose tissue may be the source of production postprandially. Disclosure N. T. Broskey: None. E. J. Demaria: None. W. J. Pories: None. J. A. Houmard: None. L. Dohm: None. T. E. Jones: None. C. J. Tanner: None. D. Zheng: None. F. Jevtovic: None. P. Krassovskaia: None. L. E. Matarese: None. R. N. Cortright: None. R. Hickner: None. Funding NIH (R01DK120296)

PSII-4 Effect of increased ruminal propionate on the expression of hepatic gluconeogenic genes in cattle on a finishing ration

Abstract The objective of this experiment was to ascertain if supplementing calcium propionate (CaP) in varying amounts would result in the increased expression of genes related to glucose metabolism in the liver. The study utilized cannulated Holstein steers (n = 6) in a 3 × 6 Latin rectangle with three 15-d periods. The treatments were as follows: Control (no CaP), low propionate (100 g/d CaP), and high propionate (300 g/d CaP). The treatments were administered in halves twice a day through rumen cannulas. The steers were provided with ad libitum finishing ration, using Insentec feeders to record feed intake and unrestricted access to water. Liver biopsies were taken on d15 of each period, a day after a glucose tolerance test, and flash frozen. RNA was extracted from the liver tissue, reverse transcribed for cDNA, and analyzed through quantitative real-time PCR. Five target genes involved in gluconeogenesis were analyzed and included solute carrier family 16 member 1 (SLC16A1), phosphoenolpyruvate carboxykinase 1 (PCK1), phosphoenolpyruvate carboxykinase 2 (PCK2), glucose-6-phosphatase (G6PC), and solute carrier family 2 member 2 (SLC2A2). Data were analyzed using a mixed model with treatment, period, and their interaction included as fixed effects and steer as a random effect. There was no treatment effect on hepatic gene expression (P ≥ 0.57). SLC16A1 showed a negative, correlation with d7 plasma lactate concentration (r = -0.84, P < 0.001) and a negative relationship with fasting plasma lactate concentration (r = -0.55, P = 0.028). SLC2A2 tended to show a positive correlation with fasting plasma glucose (r = 0.44, P = 0.09), fasting plasma lactate concentration (r = 0.43, P = 0.09), and glucose area under the curve (r = 0.46, P = 0.07). These data indicate that increased propionate may not have an impact on hepatic gene expression.

The association between lactate and muscle aerobic substrate oxidation: Is lactate an early marker for metabolic disease in healthy subjects?

Fasting plasma lactate concentrations are elevated in individuals with metabolic disease. The aim of this study was to determine if the variance in fasting lactate concentrations were associated with factors linked with cardiometabolic health even in a young, lean cohort. Young (age 22 ± 0.5; N = 30) lean (BMI (22.4 ± 0.4 kg/m2) women were assessed for waist‐to‐hip ratio, aerobic capacity (VO2peak), skeletal muscle oxidative capacity (near infrared spectroscopy; fat oxidation from muscle biopsies), and fasting glucose and insulin (HOMA‐IR). Subjects had a mean fasting lactate of 0.9 ± 0.1 mmol/L. The rate of deoxygenation of hemoglobin/myoglobin (R 2 = .23, p = .03) in resting muscle and skeletal muscle homogenate fatty acid oxidation (R 2 = .72, p = .004) were inversely associated with fasting lactate. Likewise, cardiorespiratory fitness (time to exhaustion during the VO2peak test) was inversely associated with lactate (R 2 = .20, p = .05). Lactate concentration was inversely correlated with HDL:LDL (R 2 = .57, p = .02) and positively correlated with the waist to hip ratio (R 2 = .52, p = .02). Plasma lactate was associated with various indices of cardiometabolic health. Thus, early determination of fasting lactate concentration could become a common biomarker used for identifying individuals at early risk for metabolic diseases.

229-LB: Plasma Lactate and Muscle Aerobic Substrate Oxidation: Does Elevated Lactate Precede Obesity?

Background: The incidence of metabolic diseases is rising and there is a dire need for early detection of risk in order to implement prevention. Fasting plasma lactate concentrations have been shown to be elevated in individuals with obesity and predictive of the development of T2D. An elevated lactate concentration is the product of a shift to glycolysis and a possible reduction in oxidative capacity. However, it is unknown if there are associations between lactate and oxidative capacity in healthy individuals that may predispose them to metabolic disease. Aim: The aim of this study was to determine if fasting lactate concentrations were linked with a reduction in skeletal muscle oxidative capacity in a young healthy population. Methods: Young (age 22 ± 0.5; N=30) lean (BMI (22.4 ± 0.4 kg/m2) women were screened for fasting plasma lactate. Subjects underwent assessments of body composition, aerobic capacity (VO2 peak), skeletal muscle oxidative capacity via near infrared spectroscopy (NIRS) and fasting glucose and insulin were measured for calculating HOMA-IR. Fatty acid oxidation rate was also determined in a subset of samples from skeletal muscle biopsies (vastus lateralis). Results: The women were insulin sensitive (HOMA-IR 1.1 ± 0.1) and had a mean fasting lactate of 0.9 ± 0.1 mmol/L. Time till exhaustion on the VO2 peak test was inversely associated with lactate (R2 = 0.20, p=0.05). Likewise, the rate of deoxygenated hemoglobin (NIRS) (R2 = 0.23, p=0.03) and skeletal muscle fatty acid oxidation (R2 = 0.72, p=0.004) were also inversely associated with fasting lactate. Lactate was inversely correlated with HDL:LDL (R2 = 0.57, p=0.02) and positively correlated with waist:hip (R2 = 0.52, p=0.02). Conclusion: Plasma lactate was inversely related to skeletal muscle oxidative capacity and with metabolic parameters that are risk factors for obesity and T2D. Fasting plasma lactate may thus be a biomarker for identifying healthy individuals at risk for metabolic diseases. Disclosure N.T. Broskey: None. T.E. Jones: None. Z. Yang: None. N. Khang: None. D. Zheng: None. C.J. Tanner: None. R.N. Cortright: None. J.A. Houmard: None. L. Dohm: None. Funding National Institutes of Health (DK56112, DK120296)

Plasma Lactate as a Marker for Metabolic Health

Blood lactate concentrations traditionally have been used as an index of exercise intensity or clinical hyperlactatemia. However, more recent data suggest that fasting plasma lactate can also be indicative of the risk for subsequent metabolic disease. The hypothesis presented is that fasting blood lactate accumulation reflects impaired mitochondrial substrate use, which in turn influences metabolic disease risk.

Sodium acetate protects against nicotine-induced excess hepatic lipid in male rats by suppressing xanthine oxidase activity

Fatty liver is the hepatic consequence of chronic insulin resistance (IR) and related syndromes. It is mostly accompanied by inflammatory and oxidative molecules. Increased activity of xanthine oxidase (XO) exerts both inflammatory and oxidative effects and has been implicated in metabolic derangements including non-alcoholic fatty liver disease. Short chain fatty acids (SCFAs) elicit beneficial metabolic alterations in IR and related syndromes. In the present study, we evaluated the preventive effects of a SCFA, acetate, on nicotine-induced dysmetabolism and fatty liver. Twenty-four male Wistar rats (n = 6/group): vehicle-treatment (p.o.), nicotine-treated (1.0 mg/kg; p.o.), sodium acetate-treated (200 mg/kg; p.o.) and nicotine + sodium acetate-treated groups. The treatments lasted for 8 weeks. IR was estimated by oral glucose tolerance test and homeostatic model assessment of IR. Plasma and hepatic free fatty acid, triglyceride (TG), glutathione peroxidase, adenosine deaminase (ADA), XO and uric acid (UA) were measured. Nicotine exposure resulted in reduced body weight, liver weight, visceral adiposity, glycogen content and glycogen synthase activity. Conversely, exposure to nicotine increased fasting plasma glucose, lactate, IR, plasma and hepatic TG, free fatty acid, TG/HDL-cholesterol ratio, lipid peroxidation, liver function enzymes, plasma and hepatic UA, XO and ADA activities. However, plasma and hepatic glucose-6-phosphate dehydrogenase-dependent antioxidant defense was not affected by nicotine. Concomitant treatment with acetate ameliorated nicotine-induced effects. Taken together, these results indicate that nicotine exposure leads to excess deposition of lipid in the liver by enhancing XO activity. The results also imply that acetate confers hepatoprotection and is accompanied by decreased XO activity.

Plasma lactate and leukocyte mitochondrial DNA copy number as biomarkers of insulin sensitivity in non-diabetic women.

High plasma lactate levels have been associated with reduced mitochondrial respiratory capacity and increased type 2 diabetes risk, while mitochondrial DNA (mtDNA) copy number has been proposed as a biomarker of mitochondrial function linked to glucose homeostasis. The aim of this study was to evaluate the association between circulating lactate levels and leukocyte mtDNA copy numbers with insulin secretion/sensitivity indexes in 65 Chilean non-diabetic women. mtDNA copy numbers were measured in leukocytes using qPCR and digital-droplet PCR. A 75-g Oral Glucose Tolerance Test (OGTT) was performed to calculate systemic and tissue-specific insulin sensitivity indexes, as well as insulin secretion surrogates based on plasma c-peptide. An intravenous glucose tolerance test (IVGTT; 0.3g/kg) was also carried out. Disposition indexes were calculated as the product of insulin secretion × sensitivity. Plasma levels of leptin, adiponectin, TNF-α, MCP-1, and non-esterified fatty acids were also determined. Fasting plasma lactate shows a significant association with a wide range of insulin sensitivity/resistance indexes based on fasting plasma samples (HOMA-S, adipose IR index, Revised-QUICKI, leptin-adiponectin ratio, TyG index, McAuley index and TG-to-HDL-C ratio), as well as OGTT-based measures such as the Matsuda index, the hepatic insulin resistance index, and the disposition index. Fasting plasma lactate was also positively associated with the circulating adipokines TNF-α and MCP-1. We also detected a direct association between fasting plasma lactate with leukocyte mtDNA copy numbers. The above results support the use of fasting plasma lactate, and possibly leukocyte mtDNA copy numbers, as biomarkers of reduced oxidative mitochondrial capacity, decreased hepatic insulin sensitivity, and future diabetes risk.

Enhanced hepatic glycogen synthesis and suppressed adenosine deaminase activity by lithium attenuates hepatic triglyceride accumulation in nicotine-exposed rats

Reduced liver glycogen synthesis might signify increased glucose flux towards fat synthesis and triggers hepatic triglyceride accumulation and dysmetabolism. Adenosine deaminase (ADA) reduces adenosine content which increases glycogenolysis. In the present study, we evaluate the effect of modulating glycogen synthesis and ADA by lithium chloride (LiCl) on nicotine-induced dysmetabolism. Twenty four male Wistar rats (n = 6/group) were allotted into four groups namely; vehicle-treated (po), nicotine-treated (1.0 mg/kg; po), LiCl-treated (5.0 mg/kg; po) and nicotine + LiCl-treated groups. The treatments lasted for 8 weeks. Nicotine exposure resulted in reduced body weight gain, liver weight, visceral adiposity, glycogen content and synthase. Along with increased insulin resistance (IR), fasting plasma glucose, lactate, plasma and hepatic ADA, XO, UA, and triglyceride (TG), total cholesterol (TC), free fatty acid, lipid peroxidation and liver injury markers. However, plasma and hepatic glucose-6-phosphate dehydrogenase-dependent antioxidant defenses were not affected by nicotine exposure. Concurrent treatment with LiCl normalizes all alterations with exception of hepatic TC. This result shows that enhancement of hepatic glycogen synthesis and suppression of ADA/XO/uric acid pathway by lithium can salvage the liver from nicotine-induced TG accumulation.

Feruloylated oligosaccharides from maize bran alleviate the symptoms of diabetes in streptozotocin-induced type 2 diabetic rats.

This study investigated the therapeutic effect of feruloylated oligosaccharides (FOs) extracted from maize bran on type 2 diabetic rats and its potential mechanism. Streptozotocin (STZ) induced type 2 diabetic male rats were orally administered with different levels of FOs for 8 weeks, and ferulic acid (FA) treatment was conducted as the positive control. Among all the treatments, the oral administration of 600 mg per kg bw per d FOs showed the best therapeutic effects on the diabetic rats by significantly lowering the levels of fasting plasma glucose (FPG), fasting insulin, TG, LDL-c, aspartate transaminase, creatine kinase and lactate dehydrogenase in plasma, while increasing the level of plasma HDL-c. In addition, the intake of FOs at 600 mg per kg bw per d exhibited the best antioxidant effects in the plasma, liver, kidney and heart of the diabetic rats, and the highest inhibitory effects on the formation of AGEs and CML in the organs, which might explain the alleviating effects of FOs on abdominal aorta injury observed in the current study. FOs presented better regulation effects on FPG, plasma lipid and the protection of abdominal aorta than FA under the same administered dosage. Based on these outcomes, FOs from maize bran could be beneficial for prevention or early treatment of diabetes mellitus.

Dietary acid load, metabolic acidosis and insulin resistance – Lessons from cross-sectional and overfeeding studies in humans

Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy individuals. In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Obsen) and insulin-resistant (Obres) based on hyperinsulinemic-euglycemic clamp glucose infusion rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 individuals participated in an overfeeding intervention (+1250kcal/day) for 28 days and studies repeated. Obsen and Obres were matched for adiposity (BMI and fat mass, both P=1). Fasting plasma lactate was higher in Obres (0.78 [0.63-1.14] mmol/L) compared with both lean (0.71 [0.44-0.90] mmol/L, P=0.02) and Obsen (0.67 [0.56-0.79] mmol/L, P=0.04) and not different between lean and Obsen (P=0.9). Overfeeding was characterized by an increase in dietary acid load scores PRAL (P=0.003) and NEAP (P=0.05), a reduction in GIR necessary to maintain euglycemia (P=0.03) and an increase in fasting plasma lactate (P=0.02). The change in lactate was inversely associated with the change in GIR (r=-0.36, P=0.03). Mild metabolic acidosis, measured by plasma lactate, aligns with insulin resistance independent of obesity and is induced by short-term increases in energy and dietary acid load in healthy humans. Further studies are required to determine whether buffering mild metabolic acidosis improves insulin resistance and reduces diabetes risk.

The Pattern of Parasite Density, Plasma Total Bile Acids and Lactate Dehydrogenase in Plasmodium Infected Patients in Rural Community

<b>Background to the study: </b>Pathophysiology of Plasmodium (vivax, ovale, falciparum and malariae) infection involves liver. Liver dysfunction and destruction of tissues could be indicated by the plasma level of Total Bile Acid (TBA) and Lactate Dehydrogenase (LDH). <b>Aim and Objective:</b> This work was designed to evaluate the pattern of parasite density, plasma total bile acids, and Lactate dehydrogenase in Plasmodium infected patients in rural community. <b>Materials and Methods:</b> The study was carried out in Kishi, the Headquarter of Irepo Local government area of Oyo state - Nigeria. Seven hundred and nine (709) subjects (Female: n=403: male: n=306) aged 5 to 68 years were tested for Plasmodium infection using Giemsa- thick film technique. The overall prevalence of Plasmodium infection among the seven hundred and nine subjects screened was found to be 29.1% (206) including 12.97% (92) HIV, HBsAg and anti-HCV seronagative patients and 16.1% (114) HIV, HBsAg or anti-HCV seropositive patients. Ninety two (92 (12.97%)) that were HIV, HBsAg and anti-HCV seronagative(female-58 (63.0%); male-34 (37%)) were recruited out of 206 (29.1%) that were found to be infected with plasmodium spp for the study. None of the subject was jaundiced as at the time of sample collection. Hepatitis B surface antigen (HBsAg) and anti-HCV tests were carried out by Enzyme Linked Immunozorbent Assay (ELIZA). HIV screening and confirmation were carried out by immuno-chromatographic and Immunobloting (Western blot) assays respectively. Fasting Plasma Total Bile Acids (TBA) and Lactate Dehydrogenase (LDH) were analyzed in the patients biochemically by spectrophotometry. <b>Result:</b> The result obtained showed an overall prevalence of Plasmodium infection as 29.1% (206) (female: 107 (52%); male: 99 (48%)) including 12.97% (92) (Female: 58 (63.0%) Male: 34 (37%)) that were HIV, HBsAg and anti-HCV seronagative and 16.1% (114) (Female: 61 (53.5%); Male: 53 (46.5%)) were co-infected with at least one of HIV, HBV or HCV. The plasmodium infected subjects were grouped into three based on the parasite density such as: patients with parasite density of 50-499; 500-999 and ≥1000. The mean value of the parasite density of each group was correlated with the plasma level of LDH and TBA. In all groups there was a strong positive correlation(R=1; R2 =1) between the plasma TBA, LDH and plasmodium parasite density. The pattern of parasite density obtained in the rural community studied include 45.7% had a mean parasite density of 282±12.0; 43.5% (853±31.0) and 10.9% (1130±61.0). There was also a statistical significant increase in the mean value of LDH and TBA with increase in parasite density with p<0.05. <b>Conclusion:</b> This work showed an overall prevalence of 29.1% (206) plasmodium infection including 16.1% (114) of the patients co-infected with at least one of HIV, HBV or HCV. The plasma level of LDH and TBA was also found to be positively correlated and directly proportional to the parasite density. Evaluation of these parameters is therefore recommended for effective control and management.

Evaluation of Parasite Density, Plasma Total Bile Acids, Alanine Transaminase, Lactate Dehydrogenase and CD4 in Plasmodium Infected Patients Treated with Morinda lucida (Oowo)

<i>Morinda Lucida</i> has been tested to have antimalarial and antidibetic effect among other health benefits. It is commonly used for the treatment of malaria infection in Oke-Ogun and its environs. Despite the health usefulness of this extract little has been reported about its biochemical alterations. This work was therefore designed to evaluate the parasite density, plasma total bile acids, Alanine transaminase, Lactate dehydrogenase and CD4 in Plasmodium infected patients treated with <i>Morinda Lucida</i><b> (Oowo)</b>. Sixty four(64) HIV, HBsAg and anti-HCV seronagative Plasmodium infected patients visiting traditional hoimes in Oke-Ogun the Nothern part of Oyo state Nigeria for traditional malaria cure aged 5 to 73 years classified into Female (n=34) and Male (n=30) were investigated. Hepatitis B surface antigen (HBsAg) and anti-HCV tests were carried out by Enzyme Linked Immunozorbent Assay (ELIZA). HIV screening and confirmation were carried out by immuno-chromatographic and Immunobloting (Western blot) assays respectively. Fasting Plasma Total Bile Acids (TBA), Lactate Dehydrogenase (LDH) and Alanine aminotransferase (ALT) were carried out biochemically by spectrophotometry while CD4 cell count was carried out by cytoflowmetry using Partec Cyflow machine and reagent. The tests were carried out in the control and test subjects before and after the treatment with the raw liquid extract of the leaf of <i>Morinda Lucida</i>. The result obtained showed a significantly higher mean values of falciparum parasite density and plasma ALT in the plasmodium infected test subjects than the values of the parameters obtained in plasmodium non-infected control subjects before and after treatment of the plasmodium infected subjects with the raw liquid extract of <i>Morinda lucida</i> with p<0.05. There was also a higher significant difference in the value of plasma LDH in the plasmodium infected test subjects before the administration of the extract than the result obtained in the plasmodium non-infected control subjects with p<0.05. A significantly higher value of plasma LDH was obtained in the test subjects before the treatment compared to the value of this parameter obtained in the test subjects after treatment (p<0.05). There was also a significantly higher mean value of TBA in the test subjects compared with the control after treatment (p<0.05). There was no significant alteration in the mean values of the CD4 cell count in the subjects before and after treatment and also in test compared with the control subjects. This recent work showed significant alterations in the mean values of the plasmodium parasite density, ALT, LDH, TBA in the test subjects studied due to plasmodium infection and the effectiveness of the raw liquid extract of the leaf of <i>Morinda Lucida </i>in the treatment of malaria<i>. </i>Estimation of plasmodium parasite density, plasma ALT, LDH, and TBA should be considered in the treatment of malaria using the raw liquid extract of the leaf of <i>Morinda Lucida</i>.

General anesthesia without neuromuscular blockade for a child with mitochondrial myopathy

Mitochondrial myopathies are rare diseases caused by disturbance of the mitochondrial chain of respiration or oxidative phosphorylation [1]. The mitochondria are a potential site of action for general anesthetic agents, and it is feasible that children with mitochondrial disease will respond abnormally to anesthetic drugs [2]. We experienced a case of successful management of a 2-year-old boy with mitochondrial myopathy under general anesthesia without the use of neuromuscular blockade. A 2-year-old boy weighing 10 kg and 87 cm in height, diagnosed with complex I deficiency mitochondrial myopathy by a pediatrician, was admitted for elective cochlear implantation. Neuromuscular examination showed mild muscle weakness and hypotonia, but the patient could control his head and sit alone. He During the preoperative fasting period, an intravenous cannula was inserted and a 500 ml solution containing 3% dextrose and 38.5 mEq/ L NaCl was infused at a rate of 40 ml/h to maintain glucose levels and prevent catabolism. The patient’s fasting plasma lactate and glucose levels were 0.9 mmol/L, and 90 mg/dl, respectively. Immediately before entering the operating room, the patient was premedicated with midazolam 0.03 mg/kg intravenously. Intraoperative routine monitoring included elec trocardiography, pulse oximetry, blood pressure, end-tidal capnography and esophageal temperature. Before induction, vital signs showed blood pressure 96/60 mmHg, heart rate 145 beats/min, and oxygen saturation 100%. General anesthesia was induced with 5 vol% of sevoflurane in 100% oxygen, and the patient was intubated. Anesthesia was maintained with 1.5-3 vol% of sevoflurane in 66% nitrous oxide in oxygen. No neuromuscular blocking agent was administered. Intraoperative vital signs kept showed; blood pressure 90/40-100/55 mmHg, heart rate 130-150 beats/min, end-tidal CO2 38-40 mmHg, body temperature 35.9-36.6 o C, and oxygen saturation 100%.

Fasting Plasma Lactate Concentrations in Ambulatory Elderly Patients With Type 2 Diabetes Receiving Metformin Therapy: A Retrospective Cross-sectional Study

Metformin is a worldwide accepted biguanide antidiabetic agent, and its effectiveness and benefit have already been well established. Among the side effects of metformin, lactate acidosis is the most problematic because of a high mortality rate, which impedes its use in clinical practice, especially in elderly patients with type 2 diabetes. Aging is associated with a decreased renal function and increasing comorbidities, but few data are available regarding plasma lactate levels in this unique population. In this study, we assessed fasting plasma lactate levels in ambulatory, elderly Taiwanese patients with type 2 diabetes, who were taking the drug, metformin, to identify independent risk factors for hyperlactemia in this group. Sixty-six ambulatory type 2 diabetic patients, > 80 years of age (mean, 83.6 years; range, 80-90 years), receiving metformin therapy, were enrolled, from January 2005 to September 2009, in the Diabetes Case Management Program. A further 79 younger patients (also type 2 diabetics on metformin) served as controls (mean age, 59.9 years; range, 37-79 years). Fasting serum electrolytes, creatinine, bicarbonate, glycated hemoglobin, plasma glucose and lactate levels were determined. Lactate levels did not differ between the elderly and control groups (13.2 +/- 5.2 mg/dL and 13.5 +/- 4.8 mg/dL, respectively). None of the patients fulfilled the lactic acidosis criteria. Patients in the elderly group had a significantly lower daily metformin dose, higher creatinine levels, and lower estimated creatinine clearance, compared with the control group (all p < 0.05). Estimated creatinine clearance was negatively associated with lactate levels in the elderly group (p < 0.05, r = -0.27), but not in the control group. Patients with fasting plasma glucose levels > 130 mg/dL had a 2.8-fold increased risk of developing hyperlactemia. Plasma lactate levels in ambulatory elderly patients with type 2 diabetes receiving metformin therapy did not differ from those in a younger age group. Patients with fasting plasma glucose levels > 130 mg/dL had a 2.8-fold risk of developing hyperlactemia, but none of them developed lactate acidosis.

Low plasma lactate concentration as a biomarker of an incompetent brain-pull: A risk factor for weight gain in type 2 diabetes patients

Body weight development is closely regulated by central nervous mechanisms. As has been demonstrated recently, the capability of the brain to actively demand energy from the body (brain-pull) is indispensable for the maintenance of systemic homeostasis. A deficit in this brain-pull may result in compensatory ingestive behavior followed by weight gain in the medium or long term. The aim of this study was to establish a biomarker of such an incompetent brain-pull. Since lactate is an alternative cerebral energy substrate to glucose, we investigated whether low fasting plasma lactate concentrations are associated with weight gain and increased feelings of hunger in patients with type 2 diabetes over a 3-year period. In a population based cohort study 134 type 2 diabetes patients were examined at baseline and 3-year follow-up. Plasma lactate concentrations and additional hormones associated with food intake such as e.g. insulin, or leptin, as well as psychological variables like hunger feelings before and after a standardized breakfast were measured. The relation between fasting plasma lactate concentrations and postprandial hunger as well as follow-up weight was analyzed. Low fasting plasma lactate concentrations predicted a higher 3-year follow-up weight (B=-1.268, SE=0.625, p=0.04). Moreover, low fasting plasma lactate concentrations were associated with more pronounced feelings of postprandial hunger (B=-0.406, SE=0.137, p<0.01). We conclude that low plasma lactate concentrations may represent a biomarker of an incompetent brain-pull, which is associated with weight gain and increased postprandial hunger in patients with type 2 diabetes mellitus. These results are in line with the view that plasma lactate can be used by the brain as an alternative energy substrate and thereby to some extent prevent overeating and obesity.

SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin

To investigate the potential relationship between the SLC22A2 gene polymorphism and blood lactate concentration in Shanghai Hans suffering from type 2 diabetes mellitus (T2DM). The SLC22A2 single nucleotide polymorphism (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformin-treated group (n=200) and a non-metformin-treated group (n=200). Fasting plasma lactic acid levels were measured with an enzyme-electrode assay. Biochemical indexes, including plasma alanine aminotransferase (ALT), creatinine (Cr), and glycolated hemoglobin (HbA1c), were also measured. The fasting plasma lactate concentration in the metformin-treated group was significantly higher than that in the non-metformin-treated group (1.29+/-0.45 mmol/L vs 1.18+/-0.44 mmol/L, P=0.015). Additionally, the ratio of patients with hyperlactacidemia was 8% (16/200) for the metformin-treated group and 5.5% (11/200) for the non-metformin-treated group, with no lactic acidosis found in either group. The frequency of the SLC22A2 808G/T T allele was 12.9%. Patients with the mutant genotype (TT) had a higher blood lactate concentration in the metformin-treated group than those in the non-metformin-treated group (t=2.492, P=0.013). This trend was not observed in the GG and GT genotypes when compared with metformin-treated and non-metformin-treated groups. Patients with the mutant genotype (TT) in the metformin-treated group also had a higher incidence of hyperlactacidemia compared with the GG genotype (40.0% vs 6.9%, P=0.050) in the metformin-treated group and the GG (6.0%, P=0.042) or GT (4.3%, P=0.043) genotypes in the non-metformin-treated group. In the metformin-treated group, there were significant gender differences in lactate concentrations in the TT (2.18+/-0.15 vs 1.04+/-0.27 mmol/L, P=0.008) and GG genotypes (1.40+/-0.51 vs 1.19+/-0.35 mmol/L, P=0.004). The lactate levels of women with the TT genotype were the highest in the metformin-treated group, but differences in lactate levels among the genotypes were not observed in the non-metformin-treated group. There is an 808G/T polymorphism in the SLC22A2 gene in Chinese Hans with T2DM. The 808G>T variance in the SLC22A2 gene can affect the plasma lactate level and the incidence of hyperlactacidemia in T2DM patients undergoing metformin therapy. Additionally, the female patients carrying the TT genotype are prone to lactatemia.

Modulatory Effect of Psidium Guajava Linn and Ocimum Gratissimum Linn on Lipid Profile and Selected Biochemical Indices in Rabbits Fed High Cholesterol Diet

The effect of aqueous leaf extracts of Psidium guajava(PG) and Ocimum gratissimum(OG) on fasting plasma glucose (FPG), total protein (TP), albumin (ALB), globulin (GLB), total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL) and lactate dehydrogenase (LDH) concentrations in rabbits fed high-cholesterol diet was investigated. Four groups of animals were used (n = 6). Animals in group A were fed normal laboratory pellet and water ad libitum; those in group B were fed the high-cholesterol diet (normal diet + 1% w/w cholesterol + 1% w/w vegetable oil) while those in groups C and D received a daily oral administration of 250 mg/kg body weight of the extract of Psidium guajava and Ocimum gratissimum, respectively, in addition to the high-cholesterol diet for a period of six weeks. Hypercholesterolemia, associated with hyperglycemia was induced significantly in animals in group B compared to normal control group (A) (P&lt;0.01). There were also significant increases in the levels of LDL (P&lt;0.05) and HDL (P&lt;0.01). Treatments with PG and OG reduced the plasma cholesterol level by 15% and 28%, respectively, compared to animals in Group B. PG caused a remarkable increase in HDL (69%) but a decrease in LDL (74%) levels. OG on the other hand reduced the levels of both HDL and LDL by 50% and 26%, respectively, compared to animals in Group B. While the level of HDL in the OG group was similar to that of normal controls, the LDL level was significantly higher (71%). Furthermore, both extracts reduced the associated hyperglycemia significantly (P&lt;0.05). This decrease was more pronounced in PG treated rabbits (PG; 43%, OG; 19%). In addition, OG stimulated a significant increase in the concentrations of LDH and serum protein, particularly albumin. These results show that aqueous extracts of both plants especially PG ameliorated the hypercholesterolemic and associated hyperglycemic effects of high cholesterol diet. However, OG shows possible contraindications and the safety of its ethnomedical usage warrants further investigation.

Comparison of lymphomononuclear cell energy metabolism between healthy, impaired glucose intolerance and type 2 diabetes mellitus patients

Diabetes mellitus (DM) is a complex disease that affects many systems. The most important cells of the immune system are lymphomononuclear (LMN) cells. Here, we aimed to evaluate the energy metabolism of LMN cells in patients with diabetes and impaired glucose tolerance. We measured LMN cell energy metabolism in patients with type 2 diabetes mellitus, impaired glucose tolerance (IGT) and healthy subjects. Cells were freshly isolated from peripheral blood and the subgroups were determined by flow cytometric method. Lactate production and glycogen utilization were significantly increased in the LMN cells of patients with type 2 DM and IGT when compared with healthy volunteers. No statistical difference was observed between the patients with type 2 DM and IGT. There was a significant correlation between fasting plasma glucose and lactate production in LMN cells. LMN cells changed their energy pathway in a diabetic state and preferred anaerobic glycolysis. Prediabetic range also affected energy metabolism in LMN cells. This abnormal energy production might cause dysfunction in LMN cells and the immune system in diabetic and prediabetic patients. In conclusion, we concluded that impaired glucose metabolism could change energy metabolism.

Lactate levels in Asian patients with type 2 diabetes mellitus on metformin and its association with dose of metformin and renal function

Our aims are to discover the average fasting plasma lactate level (FPL) in Asian patients with type 2 diabetes mellitus on metformin, with or without renal impairment and whether FPL is associated with the total daily dose of metformin (Tmet) and the degree of renal impairment in these patients. We conducted an observational cross-sectional study of Asian patients with type 2 diabetes, using measurements of FPL levels and glomerular filtration rate (GFR) calculated, using the abbreviated modification of diet in renal disease (MDRD) formula. The association between FPL, Tmet, GFR and other potential predictors was analysed. A total of 97 subjects were recruited from our diabetes centre between July 2005 and February 2006. Sixty (61.9%) of the subjects were males; 69 (71.1%) Chinese, 21 (21.6%) Malays and 6 (6.2%) Indians. The mean (SD) age was 58.8 years (10.7) and the mean body mass index was 27.1 kg/m(2) (5.3). The mean FPL was 1.8 mmol/l (0.9) with 20 (20.6%) of subjects having an FPL beyond the upper limit of our reference range of 2.2 mmol/l. The mean FPL (two SE) of subjects with Tmet of < or = 1000, 1001-2000 and > 2000 mg were 1.7 mmol/l (0.2), 1.6 mmol/l (0.2) and 2.1 mmol/l (0.5) respectively, (p = 0.119). The mean FPL of subjects with GFR of < 60, 60-90 and > 90 ml/min/1.73 m(2) was 1.7 mmol/l (0.3), 1.8 mmol/l (0.3) and 1.8 mmol/l (0.4) respectively, p = 0.757. Among the potential predictors analysed, aspartate transaminase (p = 0.001) was found to be significantly associated with FPL. Our study shows no correlation between Tmet and GFR with FPL in Asian type 2 diabetic patients on metformin.