c-peptide and Lung-Neoplasms

Impaired fasting glucose (IFG) is commonly seen in the US population. Approximately 20% of patients with IFG can progress to develop type 2 diabetes mellitus (DM-2) within 1 year. In the recent diabetes prevention study, lifestyle changes reduced the progression to only 8% per year, and metformin reduced the progression from IFG to DM-2 from 20% to 11% per year. Sulfonylurea therapy in DM-2 increases beta-cell function and fails to accelerate the 4% loss in function observed per year. Low-dose sulfonylurea therapy for IFG may be an effective treatment to delay the onset of type 2 diabetes if the treatment does not cause hypoglycemia. A very low dose of glyburide (20 microg/kg body weight) was given orally to 15 nondiabetic volunteers in an attempt to describe its effects on glucose production rates (GPR), blood glucose concentrations, and conterregulatory hormone profile. Six of the volunteers had IFG (mean +/- SEM, 115 +/- 1.8 mg/dL), and 9 had a normal fasting glucose (NFG) (94 +/- 2.3 mg/dL). Fasting blood glucose (FBG) decreased more in IFG after glyburide when compared with the NFG group (29% +/- 2.4% v 17% +/- 3.5%, P <.05). Patients with IFG had a larger insulin response to glyburide than those with NFG (17.7 +/-3 v 10.7 +/- 2.9 microU/mL; P <.05). The IFG patients also had a greater decrease in GPR (19% +/- 4%) than seen with the normals (12% +/- 3%, P <.05). The steeper decrease in GPR may have been due to a greater insulin response to oral glyburide in those with IFG. Low-dose glyburide increases insulin's effect on the liver.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Epinephrine; Fasting; Female; Glucose; Glucose Tolerance Test; Glyburide; Hormones; Humans; Hypoglycemic Agents; Lung Neoplasms; Male; Middle Aged; Oxidation-Reduction

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they may cause immune-related adverse events. Although there have been a few reports of new-onset type 1 diabetes mellitus (T1DM) during ICI treatment, T1DM as a delayed immune-related event after discontinuing immunotherapy is extremely rare. Herein, we report the case of an elderly veteran who presented with diabetic ketoacidosis 4 months after the discontinuation of treatment with nivolumab.. A 74-year-old veteran was treated with second-line nivolumab for advanced non-small cell lung cancer. After 9 treatment cycles, the administration was discontinued due to fatigue. Four months later, he was admitted to the emergency department in a stuporous mental state and hyperglycemia, with high glycosylated hemoglobin levels (10.6%). C-peptide levels were significantly decreased, with negative islet autoantibodies.. We diagnosed nivolumab-induced T1DM. There were no laboratory results indicating a new thyroid dysfunction or adrenal insufficiency, which are typical endocrine adverse reactions.. Since the hypothalamic and pituitary functions were preserved and only the pancreatic endocrine capacity was impaired, we administered continuous intravenous insulin injections, with fluid and electrolyte replacement.. His serum glucose levels decreased, and symptoms improved; hence, on the 8 day of hospitalization, we switched to multiple daily insulin injections.. The present case indicates that regular glucose monitoring and patient education are needed for diabetic ketoacidosis after the discontinuation of ICI therapy.

Topics: Aged; Autoantibodies; Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Carcinoma, Non-Small-Cell Lung; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Electrolytes; Glycated Hemoglobin; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Male; Nivolumab

We describe here a case of nivolumab-induced type 1 diabetes, which developed within 9 days of treatment. The case highlights the importance of frequent monitoring of glucose after initiation of nivolumab treatment.

Topics: Aged; Antineoplastic Agents, Immunological; C-Peptide; Carcinoma, Non-Small-Cell Lung; Diabetes Mellitus, Type 1; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Male; Nivolumab

C-peptide has a beneficial effect against diabetic complications, but its role in hyperglycemia-induced metastasis is unknown. We investigated hyperglycemia-mediated pulmonary vascular leakage and metastasis and C-peptide inhibition of these molecular events using human pulmonary microvascular endothelial cells (HPMVECs) and streptozotocin-induced diabetic mice. VEGF, which is elevated in the lungs of diabetic mice, activated transglutaminase 2 (TGase2) in HPMVECs by sequential elevation of intracellular Ca

Topics: Animals; Apoptosis; C-Peptide; Diabetes Mellitus, Experimental; Female; GTP-Binding Proteins; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Pathologic; Protein Glutamine gamma Glutamyltransferase 2; Reactive Oxygen Species; Transglutaminases; Vascular Endothelial Growth Factor A

Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects, especially in the endocrine system. Several cases of acute-onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible human leukocyte antigen (HLA) genotype for type 1 diabetes, possibly suggesting that HLA might be involved in the onset of diabetes with anti-PD-1 therapy. We describe an atypical case of hyperglycemia after anti-PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes and steroid diabetes was given nivolumab three times for chemoresistant adenocarcinoma of the lung. On day 5 after the third infusion of nivolumab, he had hyperglycemia (blood glucose 330 mg/dL and hemoglobin A1c 8.0%) without ketosis and with incompletely deficient insulin secretion. The patient had both type 1 diabetes susceptible (HLA-A*24:02 and -DRB1*09:01) and resistant (HLA-DRB1*15:02) HLA genotypes. These HLA genotypes differ from those previously reported in anti-PD-1 antibody-induced diabetes, and might have influenced the preservation of insulin secretion after nivolumab administration in the present case.

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; HLA Antigens; Humans; Hyperglycemia; Insulin; Insulin Secretion; Lung Neoplasms; Male; Nivolumab

Known associations between diabetes and cancer could logically be attributed to hyperglycemia, hypersecretion of insulin, and/or insulin resistance. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up.. The cohort included subjects aged 40 years and above from the Third National Health and Nutrition Examination Survey (NHANES III) with fasted serum glucose >100 mg/dl without the aid of pharmaceutical intervention (insulin or oral hypoglycemics). Cancer mortality was obtained from the NHANES III-linked follow-up database (up to December 31, 2006). A Cox regression model was applied to test for the associations between cancer mortality and fasting serum glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, insulin like growth factor (IGF-1), IGF binding protein 3 (IGFBP3) and estimated insulin resistance.. A total of 158 and 100 cancer deaths were recorded respectively from 1,348 men and 1,161 women during the mean 134-month follow-up. After adjusting for the effect of age and smoking in women, all-cause cancer deaths (HR: 1.96 per pmol/ml, 95% CI: 1.02-3.77) and lung cancer deaths (HR: 2.65 per pmol/ml, 95% CI: 1.31-5.36) were specifically associated with serum C-peptide concentrations. Similar associations in men were not statistically significant. Serum glucose, HbA1c, IGF-1, IGFBP3 and HOMA were not independently related to long-term cancer mortality.. C-peptide analyses suggest a modest association with both all-cause and lung cancer mortality in women but not in men. Further studies will be required to explore the mechanisms.

Topics: Adult; Aged; Biomarkers; C-Peptide; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prediabetic State; Prognosis; Risk Factors; Smoking; Survival Rate

Insulin-like growth factor 1 (IGF-I), IGF binding proteins (IGFBP) 1 to 7, and C-peptide have been postulated to predict survival in non-small cell lung cancer (NSCLC). Studying serum levels in NSCLC patients treated with surgical resection may provide information on the aggressiveness of tumors and be predictive of disease recurrence.. Immunobead assays were used to measure pretreatment serum levels of IGF-I, IGFBP1 to IGFBP7, and C-peptide in 100 NSCLC patients. Of these, 59 had no metastatic progression (T1 to T4 N0 M0), whereas 41 had positive lymph nodes (T1 to T4 N1 to N3 M0). Data were analyzed using the Mann-Whitney two-sided rank sum test or Kaplan-Meier curves.. Low serum IGFBP5 levels correlated strongly with a positive nodal status (p < 0.001) and any incidence of disease recurrence (p = 0.003). Low serum levels of IGFBP5 also predicted poor recurrence-free survivals in the overall cohort (p ≤ 0.001) and in patients with no nodal metastases (p = 0.027). Conversely, a high serum level of IGFBP7 correlated with positive nodal status (p = 0.008), but was not prognostic for recurrence-free survival. No significant correlations were found for IGFBP5 or IGFBP7 for sex, age, race, smoking history, tumor histology, or fasting state.. IGFBP5 and IGFBP7 had value as biomarkers for identifying NSCLC progression and patient outcome.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Peptide; Carcinoma, Non-Small-Cell Lung; Disease Progression; Female; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Lung Neoplasms; Male; Middle Aged; Prospective Studies

Patients with type 2 diabetes (DM) demonstrate inadequate insulin release, elevated gluconeogenesis, and diminished nonoxidative glucose disposal. Similar metabolic changes occur during systemic injury caused by infection, trauma, or cancer. Described here are metabolic changes occurring in 16 DM and 11 lung cancer patients (CA) and 13 normal volunteers (NV). After a 10-h overnight fast, all subjects had fasting hormone and substrate concentrations determined, along with rates of glucose production, leucine appearance (LA), and leucine oxidation (LO). Fasting insulin (data not shown) and C-peptide concentrations were elevated in DM and CA compared with weight-matched NV (0.72 +/- 0.09 and 0.64 +/- 0.08 vs. 0.51 +/- 0.03 mg/l, P < 0.05). C-reactive protein concentration was elevated in CA compared with DM and NV (23.3 +/- 6.0 vs. 4.2 +/- 1.4 and 2.1 +/- 0.5 mg/l, P < 0.01). All counterregulatory hormones were normal except for serum cortisol (11.4 +/- 1.0 and 12.1 +/- 1.0 vs. 8.9 +/- 0.7 microg/dl, DM and CA vs. NL, respectively, P < 0.05). Glucose production was increased in DM and CA compared with NV (4.22 +/- 0.6 and 3.53 +/- 0.3 vs. 2.76 +/- 0.2 mg x kg lean body wt(-1) x min(-1), P < 0.01). LO and LA were increased in DM and CA compared with NV (LO: 27.3 +/- 1.5 and 19.7 +/- 1.5 vs. 12.5 +/- 1.1 mmol x kg lean body wt(-1) x min(-1), P < 0.05; LA: 91.9 +/- 6.6 and 90.7 +/- 7.0 vs. 79.1 +/- 6.0 mmol. kg lean body wt(-1) x min(-1), P < 0.01). DM share similar metabolic derangements with CA. The increase in LA may be secondary to an increased glucose production where amino acids are mobilized to provide the liver with adequate substrate to make glucose. The increase in glucose production may also be part of the injury response, or it may represent a form of insulin resistance that exists in both the DM and (non-DM) CA patients.

Topics: Acute-Phase Reaction; Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Glucagon; Gluconeogenesis; Humans; Hydrocortisone; Insulin; Interleukin-6; Leucine; Lung Neoplasms; Middle Aged; Triiodothyronine; Tumor Necrosis Factor-alpha

Augmented glucose utilisation or secretion of insulin-like-growth-factor II (IGF-II) are discussed as important pathogenetic factors in tumor-associated hypoglycemia (Doege-Potter Syndrome) with suppressed insulin and C-peptide levels. Primary malignant fibrous histiocytoma of the lung is an uncommon neoplasia and its association with hypoglycemia is rare and the causal relationship remains unclear. - We report a 57-year-old male with spontaneous hypoglycemia (1.67 mmol/l) due to a primary malignant fibrous histiocytoma of the lung, secreting IGF-II. Insulin (0.10 nmol/l; normal range 0.33-1.2) and C-peptide (3.0 mIU/l; 5-25) levels were suppressed in combination with low levels of growth hormone (<0.5 ng/ml; <7 ng/ml) and IGF-I (<66.0 ng/ml; 70-246). The elevated IGF-II level (787 ng/ml; 300-500) and decreased IGF-binding protein 3 (1.6 mg/l; 2-5) indicated a high free IGF-II activity. After surgery (resection of the right upper lobe), glucose (4.4 mmol/l), insulin (9.0 mIU/L) and C-peptide (0.84 nmol/l) levels returned to normal. Serum IGF-I (289 ng/ml) and the IGF-I/IGF-II ratio (<0.08 preoperative vs. 0.41 postoperative; >0.20) increased to the normal reference range. - In conclusion, malignant fibrous histiocytoma (MFH) is rarely described presenting as tumor-induced hypoglycemia. Doege-Potter Syndrome in MFH seems to be related to tumor-associated IGF-II production.

Topics: Adult; C-Peptide; Histiocytoma, Benign Fibrous; Human Growth Hormone; Humans; Hypoglycemia; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Lung Neoplasms; Male; Tomography, X-Ray Computed

Haemangiopericytoma is a rare soft tissue tumour originating from the contractile pericapillary cells. Relatively little is known about its molecular pathogenesis. To address this issue, the insulin-like growth factor family (IGFs) was analysed in 19 tumours collected from a human tumour bank network. Seven of the tumours were associated with severe hypoglycaemia. Of these, six were retroperitoneal and one was located in the leg. 3 out of the 19 tumours (15.8 per cent) were positive for insulin-like growth factor I (IGF I) mRNA and 11 were positive for IGF II mRNA (57.9 per cent). Almost 90 per cent of haemangiopericytomas expressed IGF I receptor (IGF IR) mRNA (17 out of 19), five (26.3 per cent) expressed IGF binding protein 1 (IGF BP1), three (15.8 per cent) expressed IGF BP2, and four (21 per cent) exhibited IGF BP3 mRNA. All of the 14 haemangiopericytomas examined with regard to specific receptor binding were IGF IR positive, ranging from 1.2 to 16.2 per cent. Binding was much higher in IGF I/IGF IR positive tumours (15.3+/-0. 7) than in IGF I negative/IGF IR positive tumours (5.1+/-3.3). The potential role of IGF IR as a growth promoting factor in malignant haemangiopericytoma was studied using antisense oligonucleotides and monoclonal antibody alphaIR3 that specifically inhibit IGF IR synthesis or activity. 10 microM IGF IR antisense oligonucleotides significantly inhibited the growth of haemangiopericytoma cells in culture, by around 50 per cent; monoclonal antibody against IGF IR (alphaIR3) also significantly inhibited proliferation. The data suggest that IGF IR may play an important role in the genesis and progression of malignant haemangiopericytomas.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Cell Division; Child, Preschool; Female; Hemangiopericytoma; Humans; Hypoglycemia; Insulin; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Lung Neoplasms; Male; Middle Aged; Pelvic Neoplasms; Receptor, IGF Type 1; Retroperitoneal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatomedins; Tumor Cells, Cultured

Artificial hyperglycemia (AHG) used in the cancer treatment considerably increases the insulin and S-peptide content in blood, decreases the glucagon concentration and tissue glucose tolerance. The changes are reversible, have a functional character, that indicates the absence of a disbalance in hormonal mechanisms of carbohydrate metabolism control as well as marked disorders of the pancreas function. In order to achieve a wider range of indications for using AHG in complex schemes of the cancer treatment, it is necessary to take measures on optimization of the carbohydrate metabolism state which should be controlled by the suggested complex of laboratory tests.

Topics: Antineoplastic Agents; Blood Glucose; C-Peptide; Carbohydrate Metabolism; Combined Modality Therapy; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Lung Neoplasms; Stomach Neoplasms