Fasting plasma lactate as a possible early clinical marker for metabolic disease risk.

Background And Aim: Elevated fasting plasma lactate concentrations are evident in individuals with metabolic diseases. However, it has yet to be determined if these associations exist in a young, healthy population as a possible early marker for metabolic disease risk. The purpose of this study was to determine if indices of the metabolic syndrome are related to plasma lactate concentrations in this population.

Greater reliance on glycolysis is associated with lower mitochondrial substrate oxidation and insulin sensitivity in infant myogenic MSCs.

Individuals with insulin resistance and obesity display higher skeletal muscle production of nonoxidized glycolytic products (i.e., lactate), and lower complete mitochondrial substrate oxidation to CO2.

Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery.

Introduction: Roux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) that can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes.

Methods: Vastus lateralis biopsy transcriptomes were generated pre- and 1-year post-RYGB in black adult females with (T2D; = 5, age = 51 ± 6 years, BMI = 53.

Ockham's razor and the metabolic syndrome.

The broad effects of bariatric/metabolic surgery on virtually every tissue and organ system remain unexplained. Weight loss, although a major factor, does not fully account for the rapid, full, and durable remission of type 2 diabetes, return of islet function, reduction of the prevalence of cancers, increase in gray matter of the brain, and decrease in all-cause mortality. This review supports the thesis that the metabolic syndrome is not a group of separate diseases but rather multiple expressions of a shared defect in the utilization of carbohydrates and lipids.

Impaired glucose partitioning in primary myotubes from severely obese women with type 2 diabetes.

The purpose of this study was to determine whether intramyocellular glucose partitioning was altered in primary human myotubes derived from severely obese women with type 2 diabetes. Human skeletal muscle cells were obtained from lean nondiabetic and severely obese Caucasian females with type 2 diabetes [body mass index (BMI): 23.6 ± 2.

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.

Plasma lactate as a marker of metabolic health: Implications of elevated lactate for impairment of aerobic metabolism in the metabolic syndrome.

Background: Fasting lactate is elevated in metabolic diseases and could possibly be predictive of the risk of developing the metabolic syndrome.

Methods: Plasma samples were analyzed for fasting lactate to compare lean subjects, nondiabetic subjects with severe obesity, and metabolically impaired subjects. Subjects with severe obesity were studied 1 week before and 1 week to 9 months after gastric bypass surgery.

Altered tricarboxylic acid cycle flux in primary myotubes from severely obese humans.

Background/objective: The partitioning of glucose toward glycolytic end products rather than glucose oxidation and glycogen storage is evident in skeletal muscle with severe obesity and type 2 diabetes. The purpose of the present study was to determine the possible mechanism by which severe obesity alters insulin-mediated glucose partitioning in human skeletal muscle.

Subjects/methods: Primary human skeletal muscle cells (HSkMC) were isolated from lean (BMI = 23.

Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome.

Roux-en-Y gastric bypass (RYGB) is an effective way to lose weight and reverse type 2 diabetes. We profiled the metabolome of 18 obese patients (nine euglycemic and nine diabetics) that underwent RYGB surgery and seven lean subjects. Plasma samples from the obese patients were collected before the surgery and one week and three months after the surgery.

High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D.

Context: Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) ≥ 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D.

Objective: We investigated if skeletal muscle insulin sensitivity (SI) was different between well-controlled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function.

Differential acute and chronic responses in insulin action in cultured myotubes following from nondiabetic severely obese humans following gastric bypass surgery.

Background: Roux-en-Y gastric bypass (RYGB) surgery has been shown to induce positive metabolic adaptations for individuals with severe obesity (body mass index ≥40 kg/m), including improved peripheral insulin action. Although a major site of insulin action, the time course changes in skeletal muscle glucose metabolism following RYGB is unclear.

Objectives: To investigate the acute and chronic effects of RYGB surgery on insulin-stimulated glucose metabolism in cultured human primary myotubes derived from nondiabetic severely obese humans.

Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass.

Objective: Exosomes from obese adipose contain dysregulated microRNAs linked to insulin signaling, as compared with lean controls, providing a direct connection between adiposity and insulin resistance. This study tested the hypotheses that gastric bypass surgery and its subsequent weight loss would normalize adipocyte-derived exosomal microRNAs associated with insulin signaling and the associated metabolome related to glucose homeostasis.

Methods: African American female subjects with obesity (N = 6; age: 38.

Effects of meal size on the release of GLP-1 and PYY after Roux-en-Y gastric bypass surgery in obese subjects with or without type 2 diabetes.

Changes in gastrointestinal peptide release may play an important role in improving glucose control and reducing body weight following Roux-en-Y gastric bypass (RYGB), but the impact of low caloric intake on gut peptide release post-surgery has not been well characterized. The purpose of this study was to assess the relationships between low caloric intake and gut peptide release and how they were altered by RYGB. Obese females including ten normoglycemic (ON) and ten with type 2 diabetes mellitus (T2DM) (OD) were studied before, 1 week, and 3 months after RYGB.

Hyperinsulinemic syndrome: the metabolic syndrome is broader than you think.

Background: Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia. In 2011 we showed that gastric bypass (RYGB) corrects these high levels even though insulin resistance remains high, ie, the operation "dissociates" hyperinsulinemia from insulin resistance. RYGB produces reversal of T2DM along with other diseases associated with the metabolic syndrome.

Insulin sensitivity is related to glycemic control in type 2 diabetes and diabetes remission after Roux-en Y gastric bypass.

Background: After initial onset, adequate glycemic control in patients with type 2 diabetes (T2DM) presents a continuing challenge even with aggressive pharmacologic treatment, and longer disease duration is associated with poorer resolution in response to Roux-en Y gastric bypass (RYGB). Skeletal muscle insulin sensitivity is an important determinant of glycemic control. We investigated whether skeletal muscle insulin sensitivity is predictive of T2DM resolution with RYGB and is in general lower in patients with longer-duration T2DM.

Severe obesity: evidence for a deranged metabolic program in skeletal muscle?

Severe obesity is increasing at a disproportionate rate compared with milder grade obesity. Our research group has obtained evidence indicative of an "obesity metabolic program" in skeletal muscles of severely obese individuals, which may be determined genetically or epigenetically. We believe that this represents a paradigm shift in thinking about metabolic regulation in obesity.

GLP-1 response to a mixed meal: what happens 10 years after Roux-en-Y gastric bypass (RYGB)?

Background: Oral meal consumption increases glucagon-like peptide 1 (GLP-1) release which maintains euglycemia by increasing insulin secretion. This effect is exaggerated during short-term follow-up of Roux-en-y gastric bypass (RYGB). We examined the durability of this effect in patient with type 2 diabetes (T2DM) >10 years after RYGB.

Is there a metabolic program in the skeletal muscle of obese individuals?

Severe obesity (BMI ≥ 40 kg/m(2)) is associated with multiple defects in skeletal muscle which contribute to insulin resistance and a reduction in fatty acid oxidation (FAO) in this tissue. These metabolic derangements are retained in human skeletal muscle cells raised in culture. Together, these findings are indicative of a dysfunctional global metabolic program with severe obesity which is of an epigenetic or genetic origin.

Roux-en-Y gastric bypass corrects hyperinsulinemia implications for the remission of type 2 diabetes.

Context: Roux-en-Y gastric bypass (RYGB) has been shown to induce rapid and durable reversal of type 2 diabetes.

Objective: The aim of the study was to investigate a possible mechanism for the remission of type 2 diabetes after RYGB.

Design: A cross-sectional, nonrandomized, controlled study was conducted.

Duodenal-jejunal bypass surgery does not increase skeletal muscle insulin signal transduction or glucose disposal in Goto-Kakizaki type 2 diabetic rats.

Background: Duodenal-jejunal bypass (DJB) has been shown to reverse type 2 diabetes (T2DM) in Goto-Kakizaki (GK) rats, a rodent model of non-obese T2DM. Skeletal muscle insulin resistance is a hallmark decrement in T2DM. The aim of the current work was to investigate the effects of DJB on skeletal muscle insulin signal transduction and glucose disposal.

Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in a Fiber-Type Specific Manner.

Metformin is a widely used insulin-sensitizing drug, though its mechanisms are not fully understood. Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of kappaB kinasebeta (IKKbeta) in this same tissue are unknown. The aim of this study was to (1) determine the ability of metformin to attenuate IKKbeta action, (2) determine whether changes in AMPK activity are associated with changes in IKKbeta action in skeletal muscle, and (3) examine whether changes in AMPK and IKKbeta function are consistent with improved insulin signaling.

Metabolic profiling of muscle contraction in lean compared with obese rodents.

Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius muscles harvested from lean and obese Zucker rats immediately and 25 min after 15 min of one-legged electrically stimulated contraction compared with the contralateral control (rested) limbs.