High Glucagon Levels Research Articles

Comparative Effect of Insulin Resistance Reduction and Hormonal Alterations on Type 2 Diabetes Remission After Bariatric Surgery.

Background: Bariatric surgery is known to induce weight loss and diabetes remission in patients with type 2 diabetes (T2D), but the exact mechanism of glycemic normalization needs to be defined. Methods: The study included patients with BMI ≥ 35 kg/m2, obesity history ≥ 10 years, and planned bariatric surgery. At baseline and 3 and 6 months after surgery, all patients underwent anthropometric measurements, body composition and blood tests (including insulin, glucagon, and incretins during oral glucose tolerance test (OGTT)), and hyperinsulinemic euglycemic clamp tests. Diabetes remission was defined if the person reached HbA1c < 6.5% after surgery and glucose-lowering therapy withdrawal. Results: The study included 86 patients, divided into groups with no diabetes (control group, n = 44) and T2D (n = 42). Most patients with T2D reached normoglycemia at 6 months. BMI and insulin resistance (according to M-index) decreased in T2D group comparably to people without diabetes. At 6 months, people with T2D at baseline had less insulin and GLP-1 secretion and higher glucagon level during OGTT when compared to the control group. Conclusions: We conclude that weight and insulin resistance reduction is sufficient for T2D remission. The absence of insulin, glucagon, and incretin restoration is not crucial for the glucose metabolism in the short-term, but it may explain the relapse of T2D years after bariatric surgery.

LBODP066 A Conservative Approach To The Management Of Glucagon Receptor (GCCR) Mutation (Mahvash Syndrome)

Abstract Background Mahvash Syndrome a rare autosomal recessive cause of pancreatic neuroendocrine tumors (pNET) results from inactivation of GCCR. Clinically it presents with hyperglucagonemia without glucagonoma syndrome. Since described in 2008 all surviving adult cases have been managed surgically. We describe 2 related cases managed medically. Case 1 In 2015 a 52 year old female with history of an enlarged pancreas (Aunt of Case 2) presented with incidentally identified hypovascular pancreatic masses while being assessed for back pain. An EBUS-guided FNA of the pancreas demonstrated a pNET with elevated serum glucagon of 100,991 pmol/ml, and Chromogranin A of 183 ng/ml but normal C-peptide, insulin, glucose, and HbA1C. CT chest abdomen pelvis, and octreotide scan had no evidence of metastasis. Due to vague abdominal discomfort, persistently high glucagon levels and pruritis without rash she was started on somatostatin analog therapy. Given her high glucagon without glucagonoma syndrome she was referred to genetics for GCCR sequencing which was notable for homozygous c.187G&amp;gt;A p. Asp63Asn variant (subsequently reclassified as pathogenic). Her case was also reviewed at the multidisciplinary tumor board given her dominant but stable conglomerate 3.2×1.7cm pancreatic lesion (individually measuring 1.6 and 1.4cm). Continued SSA for 7 years showed a slow change in size of the pNET with the dominant lesion at the pancreatic head (1.8cm from 1.6cm in 2015), with no evidence of metastatic spread or clinical changes. Case 2 a 46 year old man with IBD and Psoriatic Arthritis, presented in 2010 with choledocholithiasis. Imaging identified a bulky pancreas with a 1.2 cm nodule consistent with a neuroendocrine tumor. His investigations included 5HIAA, Gastrin, Prolactin, Chromogranin A, Insulin, Fasting Glucose, and HgbA1C all of which were normal. In 2015 following identification of an Aunt (Case 1) with a GCCR Variant of Uncertain Significance his glucagon level was found to be above the limit of detection for the assay. Given his preferences and lack of symptoms, he was monitored clinically without surgery or medications. His Glucagon levels have remained stably elevated at 12940 pg/ml, and the initial pNET has slowly progressed to 1.3cm with an additional 1.1cm and 0.5cm pNETs identified over a 7 year interval. Conclusion These cases describe 2 patients with homozygous c.187G&amp;gt;A GCCR variants, resulting in Mahvash Syndrome. In contrast to previously published cases of the syndrome, and specifically the case report with the same variant, they have been managed non-surgically with regular imaging, and in Case 1 with SSA therapy. While there has been slow growth of the underlying pNET, there has been no clinical changes or evidence of metastatic disease, providing insight into the natural history of Mahvash Syndrome caused by c.187G&amp;gt;A variant, and possibly supporting a less aggressive clinical approach. Presentation: No date and time listed

P15.05: Safety of Once-Weekly Dulaglutide on Post-transplant Diabetes Mellitus: A Preliminary Single-Centre Experience

Introduction: Almost all immunosuppressive drugs (IS), including glucocorticoids, calcineurin and mTOR inhibitors, play a central role in the development of Post-Transplant Diabetes Mellitus (PTDM). IS potentially cause the development of a dysglycemic state, both for the direct cytotoxic action on pancreatic beta cells and for the induction of insulin resistance. PTDM is also associated with increased risk for cardiovascular disease and with worse graft and patients’ survival. Currently there are no clear recommendations on the choice of the most safe and effective anti-diabetic drug for PTDM. IS are linked with several pharmacokinetic interactions and burdened with vary degree of nephrotoxicity. Glucagon like peptide- 1 receptor agonists (GLP1RA) are largely used for the treatment of type 2 diabetes. They act stimulating endogenous insulin secretion in a glucose-dependent manner. GLP1RAs reduce blood sugar by stimulating insulin release, suppressing high glucagon levels, delaying gastric emptying, and reducing food intake. Furthermore, GLP1 has been shown to promote proliferation of beta cells in animal models. GLP1RA has proven to be safe and effective in reducing HbA1c without directly causing hypoglycemia and has shown a clear association with cardiovascular risk reduction and renal protection. Despite GLP1RA seems to act with a mechanism that perfectly contrasts the pathogenetic aspects of PTDM, in the literature clinical experience is entirely limited to case series and retrospective studies. Method: In order to assess primarily safety of GLP1RA therapy in patients with PTDM we have prospectively enrolled a sample of N = 20 patients referred to liver (N = 10), renal (N = 5), as well as heart (N = 4) and lung (N = 1) transplant at ISMETT. All patients were placed on once-weekly dulaglutide therapy. Weight, HbA1c Level, as well as complete lipid profile and liver function tests were performed at 3 months and again at 6 months. One-way Repeated measurements ANOVA was used to test significant change in collected variables over time. Results: The study was closed at 6 months follow-up visit. Mild gastrointestinal symptoms were experienced by patients at the treatment start and resolved in 2 weeks. There were no persistent side effects due to dulaglutide in our study population and all recruited patients were on dulaglutide at 6 months evaluation. Body weight, Total cholesterol, Fibrosis-4 Index, alanine aminotransferase and aspartate aminotransferase levels were all reduced at the end of the follow-up, while blood glucose as well as HbA1c were stable over time (Table 1, Figure 1). Conclusion: Dulaglutide has proven to be safe in a population of transplanted patients with PTDM. In addition, a significative reduction of metabolic parameters was found. GLP1RA could be a preferred treatment for patients with PTDM considering also the extraglycemic effects of cardiovascular and renal protection.

Role of the Gut Microbiota in Glucose Metabolism During Heart Failure.

BackgroundBlood glucose disorders are prevalent in heart failure, while the influence of the gut microbiota on this process remains unclear. Here, we used heart failure model mice and fecal microbiota transplantation (FMT) mice to evaluate the effect of the gut microbiota on the regulation of blood glucose during heart failure.MethodsThoracic aortic constriction (TAC) surgery was performed in a heart failure model, while an antibiotic cocktail was used to eliminate the microbiota to establish a germ-free (GF) model. Blood glucose, insulin, and glucagon levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed. 16S rRNA sequencing and metabolomics were used to evaluate the changes in gut microbiota structure and metabolism induced by TAC. Another group of FMT mice was established to observe the effect of the gut microbiota on host metabolism.ResultsAfter microbiota clearance, the glucagon concentration, the homeostasis model assessment for insulin resistance (HOMA-IR), and the area under the curve (AUC) of the IPGTT were decreased significantly in the TAC germ-free (TAC-GF) group in the third month as compared to the other groups. 16S rRNA sequencing indicated that TAC surgery affected the gut microbiota structure, and fecal metabolomics suggested that noradrenaline and adrenaline levels were higher in the TAC group than in the sham group. The FMT mice transplanted with the feces of the TAC (FMT-TAC) mice displayed a higher AUC of IPGTT, accompanied by a higher glucagon level, insulin level, and HOMA-IR than those of the mice in the other groups. The serum metabolomics of the FMT-TAC group showed that noradrenaline levels were significantly higher than those of the FMT-sham group.ConclusionThe gut microbiota and its metabolism were altered during heart failure, which increased blood glucose and glucagon in the host.

Necrolytic migratory erythema is an important visual cutaneous clue of glucagonoma

Glucagonoma is an extremely rare neuroendocrine tumor that arises from pancreatic islet alpha cells. Although glucagonoma is usually accompanied by a variety of characteristic clinical symptoms, early diagnosis is still difficult due to the scarcity of the disease. In this study, we present the cumulative experiences, clinical characteristics and treatments of seven patients diagnosed with glucagonoma during the past 10 years at the First Affiliated Hospital of Xi’an Jiaotong University. The seven patients in our cohort consisted of six females and one male with an average diagnosis age of 40.1 years (range 23–51). The average time from onset of symptoms to diagnosis of glucagonoma was 14 months (range 2–36 months). All the patients visited dermatology first for necrolytic migratory erythema (NME) 7/7 (100%), and other presenting symptoms included diabetes mellitus (DM) 4/7 (57%), stomatitis 2/7 (28%), weight loss 4/7 (57%), anemia 4/7 (57%), diarrhea 1/7 (14%), and DVT1/7 (14%). Plasma glucagon levels were increased in all patients (range 216.92–3155 pg/mL) and declined after surgery. Imaging studies revealed that four of seven patients had liver metastasis. Six of seven patients received surgical resection, and all of them received somatostatin analog therapy. Symptoms improved significantly in 6 out of 7 patients. Three of seven patients died of this disease by the time of follow-up. Our data suggest that if persistent NME is associated with DM and high glucagon levels, timely abdominal imaging should be performed to confirm glucagonoma. Once diagnosed, surgery and somatostatin analogs are effective for symptom relief and tumor control.

FOXA2 prevents hyperbilirubinaemia in acute liver failure by maintaining apical MRP2 expression

ObjectiveMultidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) that is closely associated...

Glucose metabolism in amyotrophic lateral sclerosis: it is bitter-sweet.

Glucose metabolism in amyotrophic lateral sclerosis: it is bitter-sweet.

Hyperglucagonemia and impaired insulin sensitivity are associated with development of prediabetes and type 2 diabetes - A study from South India

Background and aimsGlucagon levels and glucagon suppression in response to oral glucose load has not been elucidated at different stages of glucose intolerance in India. MethodsA total of 81 subjects underwent OGTT and were classified into three groups as having normal glucose tolerance (NGT) (n = 23), prediabetes (PreDM) (n = 33), newly diagnosed diabetes (NDM) (n = 25). Insulin and glucagon at fasting, 30 and 120 min was measured by ELISA. HOMA-IR, measures of insulin sensitivity, early, late and overall glucagon suppression during OGTT was calculated. ResultsPlasma glucagon levels were higher at all-time points in the PreDM and NDM groups. Fasting glucagon levels were higher than post glucose load glucagon in all groups. There was a significant difference in the fasting(p = 0.001), 30 min(p = 0.004) and 120 min(p = 0.032) glucagon between the groups. HOMA-IR increased and insulin sensitivity decreased with worsening of glucose intolerance(p < 0.0001). The groups did not differ in terms of early glucagon suppression(p = 0.094). NDM group suppressed glucagon more than NGT from 30 to 120 min after glucose intake. ConclusionThis study demonstrated higher fasting glucagon levels. Prediabetes and newly diagnosed diabetes individuals had higher glucagon levels, high insulin resistance and lower insulin sensitivity. Hyperglucagonemia may contribute to type 2 diabetes.

Glucagonoma: how the misdiagnosis of a paraneoplastic cutaneous manifestation affects the clinical outcome: a case report

Background: Glucagonoma is a rare functional pancreatic neuroendocrine tumor. Necrolytic migratory erythema (NME) is a paraneoplastic manifestation of glucagonoma and is often the first presenting symptom. The misdiagnosis of this rare entity can affect the patient’s quality of life and his life expectancy. Case Presentation: We report a case of a 48-year-old man presenting with pruritic scaly rash, ulcerated skin lesions, and periorbital edema, who was diagnosed and treated for atopic eczema for a 7-year period. Despite treatment, his dermatitis and general conditions progressively worsened, until he was admitted to the emergency department due to weight loss and fatigue. An uncontrolled diabetes was found and the computer tomography scan of the abdomen revealed a tumor located in the tail of the pancreas with liver metastases. Subsequently, liver biopsy and high levels of glucagon confirmed the diagnosis of glucagonoma. The patient was treated with short-acting subcutaneous octreotide for 2 weeks and then with intramuscular slow-release octreotide every 28 days, with a significant improvement of the symptoms. Conclusion: This case provides further knowledge about NME, since a timely recognition and treatment of this misleading disease can prevent morbidity from the dermatitis and mortality from the malignancy itself.

Paracrine control of \u03b1-cell glucagon exocytosis is compromised in human type-2 diabetes

Glucagon is released from pancreatic α-cells to activate pathways that raise blood glucose. Its secretion is regulated by α-cell-intrinsic glucose sensing and paracrine control through insulin and somatostatin. To understand the inadequately high glucagon levels that contribute to hyperglycemia in type-2 diabetes (T2D), we analyzed granule behavior, exocytosis and membrane excitability in α-cells of 68 non-diabetic and 21 T2D human donors. We report that exocytosis is moderately reduced in α-cells of T2D donors, without changes in voltage-dependent ion currents or granule trafficking. Dispersed α-cells have a non-physiological V-shaped dose response to glucose, with maximal exocytosis at hyperglycemia. Within intact islets, hyperglycemia instead inhibits α-cell exocytosis, but not in T2D or when paracrine inhibition by insulin or somatostatin is blocked. Surface expression of somatostatin-receptor-2 is reduced in T2D, suggesting a mechanism for the observed somatostatin resistance. Thus, elevated glucagon in human T2D may reflect α-cell insensitivity to paracrine inhibition at hyperglycemia.

Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis.

Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role and that hepatic amino acid metabolism and glucagon are linked in a mutual feedback cycle, the liver-α-cell axis. On the basis of this knowledge, we hypothesized that hepatic steatosis might impair glucagon's action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia. We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism when glucagon was at basal levels and at high physiological levels. The degree of steatosis was evaluated from liver biopsy specimens. Total RNA sequencing of liver biopsy specimens from the obese steatotic individuals revealed perturbations in the expression of genes predominantly involved in amino acid metabolism. This group was characterized by fasting hyperglucagonemia, hyperaminoacidemia, and no lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals. Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism. This results in increased amino acid concentrations and increased glucagon secretion, providing a likely explanation for fatty liver-associated hyperglucagonemia.

Study of Possible Relation between Fasting Plasma Glucagon, Gestational Diabetes and Development of Type 2 DM.

Women who develop GDM (gestational diabetes mellitus) have a relative insulin secretion deficiency, the severity of which may be predictive for later development of diabetes. This study aimed to investigate the role of fasting plasma glucagon in the prediction of later development of diabetes in pregnant women with GDM. The study was conducted on 150 pregnant women with GDM after giving informed oral and written consents and being approved by the research ethical committee according to the declaration of Helsinki. The study was conducted in two phases, first phase during pregnancy and the second one was 6 months post-partum, as we measured fasting plasma glucagon before and after delivery together with fasting and 2 hour post-prandial plasma sugar. Our findings suggested that glucagon levels significantly increased after delivery in the majority 14/25 (56%) of GDM women who developed type 2 DM within 6 months after delivery compared to 6/20 (30%) patients with impaired fasting plasma glucose (IFG) and only 22/105 (20%) non DM women, as the median glucagon levels were 80,76, 55, respectively. Also, there was a high statistical difference between fasting plasma glucagon post-delivery among diabetic and non-diabetic women (p ≤ 0.001). These results indicated the useful role of assessing fasting plasma glucagon before and after delivery in patients with GDM to predict the possibility of type 2 DM. There is a relatively high glucagon level in GDM patients, which is a significant pathogenic factor in the incidence of subsequent diabetes in women with a history of GDM. This could be important in the design of follow-up programs for women with previous GDM.

Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice.

While the autoimmune character of T1D (type 1 diabetes) is being challenged, it is currently recognized that inflammation plays a key role in its development. We hypothesized that glucotoxicity could contribute to β-cell mass destruction through participation in islet inflammation. We evaluated the potential of empagliflozin (EMPA) and GABA (gamma-aminobutyric acid) to protect β-cell mass against glucotoxicity and to increase β-cell mass after diagnosis of T1D. Empagliflozin is a SGLT2 (sodium-dependent glucose cotransporter) inhibitor which thereby blocks glucose recapture by the kidney and promotes glucose excretion in urine. GABA is an inhibitory neurotransmitter, which stimulates α-to-β cell transdifferentiation. In streptozotocin-treated mice, empagliflozin and/or GABA were delivered for a period of five days or three weeks. As compared to untreated T1D mice, EMPA-treated T1D mice had decreased FFA (free fatty acid) levels and improved glucose homeostasis. EMPA-treated T1D mice had higher islet density, with preserved architecture, compared to T1D mice, and EMPA-treated T1D mice also differed from T1D mice by the total absence of immune cell infiltration within islets. Islets from EMPA-treated mice were also less subjected to ER (endoplasmic reticulum) stress and inflammation, as shown by qPCR analysis. Glucose homeostasis parameters and islet area/pancreas area ratio improved, as compared to diabetic controls, when T1D mice were treated for three weeks with GABA and EMPA. T1D EMPA+GABA mice had higher glucagon levels than T1D mice, without modifications of glucagon area/islet area ratios. In conclusion, empagliflozin and GABA, used in monotherapy in streptozotocin-induced diabetic mice, have positive effects on β-cell mass preservation or proliferation through an indirect effect on islet cell inflammation and ER stress. Further research is mandatory to evaluate whether empagliflozin and GABA may be a potential therapeutic target for the protection of β-cell mass after new-onset T1D.

1976-P: Physiological Effects of GIP(1-30)NH2 in Healthy Subjects

The gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) circulates in at least two active forms: GIP(1-42), which besides its insulinotropic effect during hyperglycemia stimulates glucagon secretion at low plasma glucose (PG) levels and decreases bone resorption, and GIP(1-30)NH2. In vitro and rodent studies has shown similar physiological effects of GIP(1-30)NH2 and GIP(1-42), but effects in humans remain unexplored. Here, we infused GIP(1-42) and GIP(1-30)NH2 in humans to establish the physiological effects of GIP(1-30)NH2. On three separate days, 10 healthy men (mean age 23 (range 20-28) years, BMI 22.4 (20.0-25.2) kg/m2) received intravenous infusions of GIP(1-42), GIP(1-30)NH2 and saline, respectively. Both peptides were infused at 4 pmol/kg/min during 200 minutes. After 20 minutes of infusion, PG was clamped at the fasting PG level (FPG) for 60 minutes, followed by 60 minutes at FPG × 1.5, and lastly 60 minutes at FPG × 2. There were no differences in PG levels between the three interventions, but significantly more glucose was needed for the clamp with GIP(1-42) compared to saline (P = 0.022). Plasma levels of GIP(1-30)NH2 reached a mean (± SD) of 31.4 ± 29.9 pmol/l and GIP(1-42) of 97.8 ± 27.9 pmol/l. Despite this difference, both infusions resulted in robust and glucose-dependent insulin responses (as assessed by serum C-peptide) with no differences between the two peptide infusions (P = 0.187), and at FPG level only GIP(1-30)NH2 resulted in higher glucagon levels than saline (P = 0.0302). At 180 minutes, the bone resorption marker carboxy-terminal collagen I crosslinks (CTX) was suppressed to 61 ± 13% of baseline values during saline, 42 ± 16% during GIP(1-30)NH2, and 29 ± 6% during GIP(1-42) (P &amp;lt; 0.001). We conclude that, like GIP(1-42), GIP(1-30)NH2 is a potent insulinotropic (at high PG levels), glucagonotropic (at low PG levels) and bone resorption-inhibiting hormone in healthy subjects. Disclosure L.S.L. Krogh: None. L.S. Gasbjerg: Stock/Shareholder; Self; Antag Therapeutics. S. Stensen: None. K. Skov-Jeppesen: None. M.M. Rosenkilde: Consultant; Self; Antag Therapeutics. B. Hartmann: None. T. Vilsbøll: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp &amp; Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp &amp; Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.

Separate and Combined Glucometabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1 in Healthy Individuals.

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted postprandially and contribute importantly to postprandial glucose tolerance. In this study, we assessed the individual and combined contributions of endogenous GIP and GLP-1 to the postprandial changes in glucose and glucoregulatory hormones using the novel GIP receptor antagonist GIP(3-30)NH2 and the well-established GLP-1 receptor antagonist exendin(9-39)NH2 During 4-h oral glucose tolerance tests (75 g) combined with an ad libitum meal test, 18 healthy men received on four separate days in randomized, double-blinded order intravenous infusions of A) GIP(3-30)NH2 (800 pmol/kg/min) plus exendin(9-39)NH2 (0-20 min: 1,000 pmol/kg/min; 20-240 min: 450 pmol/kg/min), B) GIP(3-30)NH2, C) exendin(9-39)NH2, and D) saline, respectively. Glucose excursions were significantly higher during A than during B, C, and D, while glucose excursions during B were higher than during C and D. Insulin secretion (assessed by C-peptide/glucose ratio) was reduced by 37 ± 16% (A), 30 ± 17% (B), and 8.6 ± 16% (C) compared with D (mean ± SD). A and C resulted in higher glucagon levels and faster gastric emptying. In conclusion, endogenous GIP affects postprandial plasma glucose excursions and insulin secretion more than endogenous GLP-1, but the hormones contribute additively to postprandial glucose regulation in healthy individuals.

The pre-operation of the cesarean of the patients with the load of carbohydrate effect on the insulin resistance and the blood glucose level of the newborn

Objective To evaluate the comfort satisfaction and the insulin resistance of patients with cesarean section and the effects of the postoperative blood sugar on the newborns during the operation. Methods Forty patients who were got elective C-section were selected and divided randomly into two groups(n=20): oral carbohydrate group(CHO group), oral placebo group(P group). Both groups used epidural anesthesia, and a routine preoperative fasting 300 ml carbohydrate drinks(it contains 14.1 g of carbohydrates per 100 ml of drink) was administrated orally 2 h before anesthesia in oral CHO group. Patients in oral placebo group were given an equal amount distilled water instead of carbohydrate. The levels of blood glucose, plasma insulin and glucagons were tested after 2 h and after fetus delivery. According to levels of blood glucose and insulin, homeostasis model assessment(HOME) was applied to calculate the index of insulin resistance(HOMA-IR) and insulin sensitivity index(HOMA-ISI). After fetus delivery, neonates blood glucose was tested immediately. Meanwhile, the subjective comfort satisfaction of the two groups patients were also tested. Results After fetus delivery, blood glucose levels of two groups were significantly elevated than the levels of 2 h after loading(P<0.05). But there is no difference of blood glucose levels between two groups. Compare with levels of 2 h after loading, patients in P group had higher insulin levels, elevated HOMA-IR levels and lower HOME-ISI levels than levels of patients in CHO group (P<0.05). Patients in P group had higher glucagon levels that patients in CHO group. Patients in CHO group have less sense of hunger. Patients of two groups have no difference on sense of vomiting. The neonates blood glucose levels in the CHO group was higher than those in P group(P<0.05). Apgar scores of newborns in two groups are not different. Conclusions C-section preoperative oral intake of carbohydrate can safely reduce the insulin resistance and relieve the feelings of thirst, and help to raise blood glucose levels in newborns. Key words: Csection; Carbohydrate; Insulin resistance; Newborn; Blood glucose

The Ketogenic Diet Alters Endocrine Regulation of Energy Metabolism in Ultra‐Endurance Athletes

PurposeThe ketogenic diet induces a profound shift in energy metabolism from carbohydrate oxidation towards fat oxidation, both at rest and during exercise. We compared endocrine regulators of energy metabolism in keto‐adapted and non‐keto‐adapted ultra‐endurance athletes before, during, and after aerobic exercise to better understand the role of endocrine function in adaptation to a ketogenic diet (keto‐adaptation).MethodsTwenty elite ultra‐endurance athletes (male, age 33.5 ± 6.4 yr, BMI 22.1 ± 1.5 kg/m2, VO2max 64.5 ± 4.9 mL/kg/min) who habitually consumed a high‐carbohydrate (HC, 59:14:25 % carbohydrate:protein:fat) or very‐low carbohydrate (LC, 10:19:70) diet for at least 6 months ran on a treadmill for 180 min at 64% of VO2max. Glucagon, cortisol, and leptin were measured from serum collected before exercise (BL); 60 and 120 min after initiation of exercise (RUN60, RUN120); and 0, 60, and 120 min after completion of exercise (IP, P60, P120). After BL and IP, participants consumed a shake with macronutrient ratios similar to their habitual diet (5 kcal/kg body mass, HC: 50:36:14, LC: 5:81:14 % carbohydrate:protein:fat). Glucagon, cortisol, and leptin were further analyzed for correlations with non‐esterified fatty acids (NEFA), glycerol, β‐hydroxybutyrate, total ketones, insulin, glucose, and muscle glycogen.ResultsGlucagon increased with exercise (p&lt;0.0001) and was significantly higher in keto‐adapted athletes at all time points except IP and P120 (p&lt;0.05). Cortisol also increased with exercise (p&lt;0.0001) and was significantly higher in keto‐adapted athletes at RUN60 (p&lt;0.05). Leptin decreased with exercise (p&lt;0.0001), but without any significant effect of diet. Glucagon and, to a lesser extent, cortisol positively correlated with markers of increased fat oxidation (β‐hydroxybutyrate, total ketones, NEFA, and glycerol, p&lt;0.05) and negatively correlated with markers of increased carbohydrate metabolism (glucose, insulin, and lactate, p&lt;0.05). Glucagon's correlations with β‐hydroxybutyrate and total ketones were persistent, occurring at all time points except BL (p&lt;0.01). Glucagon and cortisol also positively correlated with each other at P120 (p&lt;0.005). Muscle glycogen content negatively correlated with glucagon at IP (p&lt;0.05) and positively correlated with leptin at P120 (p&lt;0.05).ConclusionIn elite ultra‐endurance athletes, a long‐term ketogenic diet is associated with higher glucagon levels before, during, and after aerobic exercise. This is in conjunction with a more than two‐fold higher rate of peak fat oxidation, indicating glucagon may have an important role in keto‐adaptation. The similar but less persistent patterns of cortisol suggest these two hormones may contribute to keto‐adaptation in a coordinated manner.Support or Funding InformationSupport for this work was provided by Quest Nutrition and The Robert C. and Veronica Atkins Foundation.

Ketoalkalosis: Masked Presentation of Diabetic Ketoacidosis With Literature Review

Most dreaded complication in type 1 diabetes mellitus remains diabetic ketoacidosis (DKA): plasma blood glucose &gt; 250 mg/dL, serum bicarbonate &lt; 18 mEq/L, anion gap metabolic acidosis and ketosis. Insulin deficiency with high levels of glucagon and stress hormones causing ketogenesis in liver, elevated lipolysis in peripheral tissues, and increased free fatty acids contribute the formation of ketones leading to metabolic acidosis. And hence DKA is also termed as ketoacidosis. Unusually, patients with diuretic use, alkali ingestion, intractable vomiting, or hypercortisolism may present with alkalemia in DKA. Contraction (Metabolic) Alkalosis masquerades metabolic acidosis with anion gap and low to normal bicarbonate that uncovers on provision of intravenous fluids. We present a case of a 25-year-old female with DKA presenting with intractable vomiting, alkalotic pH and high anion gap. J Endocrinol Metab. 2017;7(6):194-196 doi: https://doi.org/10.14740/jem472w

Ketoalkalosis: Masked Presentation of Diabetic Ketoacidosis With Literature Review

Most dreaded complication in type 1 diabetes mellitus remains diabetic ketoacidosis (DKA): plasma blood glucose > 250 mg/dL, serum bicarbonate < 18 mEq/L, anion gap metabolic acidosis and ketosis. Insulin deficiency with high levels of glucagon and stress hormones causing ketogenesis in liver, elevated lipolysis in peripheral tissues, and increased free fatty acids contribute the formation of ketones leading to metabolic acidosis. And hence DKA is also termed as ketoacidosis. Unusually, patients with diuretic use, alkali ingestion, intractable vomiting, or hypercortisolism may present with alkalemia in DKA. Contraction (Metabolic) Alkalosis masquerades metabolic acidosis with anion gap and low to normal bicarbonate that uncovers on provision of intravenous fluids. We present a case of a 25-year-old female with DKA presenting with intractable vomiting, alkalotic pH and high anion gap. J Endocrinol Metab. 2017;7(6):194-196 doi: https://doi.org/10.14740/jem472w

Factors modulating food intake and energy expenditure prior to liver transplantation

ABSTRACT Background . There is a high prevalence of nutritional disorders in patients with liver cirrhosis (LC). This study was designed to assess the relationships between liver function, IFG-I/IGFBP-3, nutritional status, leptin, ghrelin and glucagon in 21 patients waiting for liver transplantation (LT). Methods. We studied 21 men aged 56 + 2.1 years who were on the LT list. They were classified according to Child-Pugh (CP) score from low to high liver dysfunction in CPA (n=4), CPB (n=11) and CPC (n=6). Body mass index (BMI) was calculated and body fat (%) was measured by air-displacement plethysmography. Resting energy expenditure (REE) and its variation over Harris-Benedict values (GER%) was assessed by indirect calorimetry. Fasting serum samples were taken to measure albumin, glucose, insulin, HbA1c, leptin, total ghrelin, glucagon, IGF-I and IGFBP3. Results . There were no differences in fat % and leptin values in the three groups according to CP classification. The CPC group showed higher ghrelin values than CPA and CPB (p<0.05). All groups displayed high glucagon levels and GER% values superior to 100%. Positive correlations were found between glucagon and GER% (r=0.56; p<0.01) and between glucagon and ghrelin values (r=0.66; p<0.01). IGF-I and IGFBP3 were low in all groups and showed a positive correlation with plasma albumin (r=0.52; p<0.05 and r=0.45; p<0.05 respectively). Conclusions . These results show an increase in ghrelin plasma values in patients with severe liver dysfunction. Hyperglucagonemia was correlated with GER%, supporting a role of glucagon in the hypermetabolic state associated to LC, raising the possibility of becoming a therapeutic target. The measurement of IGF-I/IGFBP3 represents a good marker of liver function in patients with LC. Key words. Liver cirrhosis. Leptin. Ghrelin. Glucagon. IGF-I