Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.Insulin-Secreting Cells: A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.Glycemic Index: A numerical system of measuring the rate of BLOOD GLUCOSE generation from a particular food item as compared to a reference item, such as glucose = 100. Foods with higher glycemic index numbers create greater blood sugar swings.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Hemoglobin A, Glycosylated: Minor hemoglobin components of human erythrocytes designated A1a, A1b, and A1c. Hemoglobin A1c is most important since its sugar moiety is glucose covalently bound to the terminal amino acid of the beta chain. Since normal glycohemoglobin concentrations exclude marked blood glucose fluctuations over the preceding three to four weeks, the concentration of glycosylated hemoglobin A is a more reliable index of the blood sugar average over a long period of time.Blood Glucose: Glucose in blood.Hypoglycemic Agents: Substances which lower blood glucose levels.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Hyperglycemia: Abnormally high BLOOD GLUCOSE level.Delayed-Action Preparations: Dosage forms of a drug that act over a period of time by controlled-release processes or technology.Octreotide: A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.Diabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.Insulin, Long-Acting: Insulin formulations that contain substances that retard absorption thus extending the time period of action.Blood Glucose Self-Monitoring: Self evaluation of whole blood glucose levels outside the clinical laboratory. A digital or battery-operated reflectance meter may be used. It has wide application in controlling unstable insulin-dependent diabetes.Hypoglycemia: A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.Sterilization, Reproductive: Procedures to block or remove all or part of the genital tract for the purpose of rendering individuals sterile, incapable of reproduction. Surgical sterilization procedures are the most commonly used. There are also sterilization procedures involving chemical or physical means.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Albuterol: A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.Nadolol: A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for MIGRAINE DISORDERS and for tremor.Insulin Infusion Systems: Portable or implantable devices for infusion of insulin. Includes open-loop systems which may be patient-operated or controlled by a pre-set program and are designed for constant delivery of small quantities of insulin, increased during food ingestion, and closed-loop systems which deliver quantities of insulin automatically based on an electronic glucose sensor.Diabetic Diet: A diet prescribed in the treatment of diabetes mellitus, usually limited in the amount of sugar or readily available carbohydrate. (Dorland, 27th ed)Diabetes Mellitus: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.Bronchodilator Agents: Agents that cause an increase in the expansion of a bronchus or bronchial tubes.Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)Ethanolamines: AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.Dietary Carbohydrates: Carbohydrates present in food comprising digestible sugars and starches and indigestible cellulose and other dietary fibers. The former are the major source of energy. The sugars are in beet and cane sugar, fruits, honey, sweet corn, corn syrup, milk and milk products, etc.; the starches are in cereal grains, legumes (FABACEAE), tubers, etc. (From Claudio & Lagua, Nutrition and Diet Therapy Dictionary, 3d ed, p32, p277)Sulfonylurea CompoundsParaneoplastic Endocrine Syndromes: Syndromes resulting from inappropriate production of HORMONES or hormone-like materials by NEOPLASMS in non-endocrine tissues or not by the usual ENDOCRINE GLANDS. Such hormone outputs are called ectopic hormone (HORMONES, ECTOPIC) secretion.Long-Acting Thyroid Stimulator: An immunoglobulin G, often found in the blood of hyperthyroid individuals. It stimulates the thyroid for a longer duration than does thyrotoxin and may cause hyperthyroidism in newborns due to placental transmission.Insulin Lispro: Insulin that has been modified so that the B-chain contains a LYSINE at position 28 instead of a PROLINE and a PROLINE at position 29 instead of a LYSINE. It is used to manage BLOOD GLUCOSE levels in patients with TYPE 2 DIABETES.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Glucose Tolerance Test: A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).Insulin, Isophane: An intermediate-acting INSULIN preparation with onset time of 2 hours and duration of 24 hours. It is produced by crystallizing ZINC-insulin-PROTAMINES at neutral pH 7. Thus it is called neutral protamine Hagedorn for inventor Hans Christian Hagedorn.Contraceptive Agents, Female: Chemical substances or agents with contraceptive activity in females. Use for female contraceptive agents in general or for which there is no specific heading.Postprandial Period: The time frame after a meal or FOOD INTAKE.Administration, Inhalation: The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Oxprenolol: A beta-adrenergic antagonist used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Fructosamine: An amino sugar formed when glucose non-enzymatically reacts with the N-terminal amino group of proteins. The fructose moiety is derived from glucose by the "classical" Amadori rearrangement.C-Peptide: The middle segment of proinsulin that is between the N-terminal B-chain and the C-terminal A-chain. It is a pancreatic peptide of about 31 residues, depending on the species. Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. C-peptide immunoassay has been used to assess pancreatic beta cell function in diabetic patients with circulating insulin antibodies or exogenous insulin. Half-life of C-peptide is 30 min, almost 8 times that of insulin.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Diabetes Complications: Conditions or pathological processes associated with the disease of diabetes mellitus. Due to the impaired control of BLOOD GLUCOSE level in diabetic patients, pathological processes develop in numerous tissues and organs including the EYE, the KIDNEY, the BLOOD VESSELS, and the NERVE TISSUE.Insulin Receptor Substrate Proteins: A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.Adrenergic beta-2 Receptor Agonists: Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS.Glucagon-Like Peptide 1: A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Somatostatin: A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.Insulin Aspart: Insulin that has been modified to contain an ASPARTIC ACID instead of a PROLINE at position 38 of the B-chain.Fasting: Abstaining from all food.Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Anti-Asthmatic Agents: Drugs that are used to treat asthma.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Infusions, Subcutaneous: The administration of liquid medication or nutrients under the skin, usually over minutes or hours.Dipeptidyl-Peptidase IV Inhibitors: Compounds that suppress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.Asthma: A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).Diabetic Angiopathies: VASCULAR DISEASES that are associated with DIABETES MELLITUS.Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.Peak Expiratory Flow Rate: Measurement of the maximum rate of airflow attained during a FORCED VITAL CAPACITY determination. Common abbreviations are PEFR and PFR.Insulin Antibodies: Antibodies specific to INSULIN.Risperidone: A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.Glucose Clamp Technique: Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.Thiazolidinediones: THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Glucagon: A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)Insulin Antagonists: Compounds which inhibit or antagonize the biosynthesis or action of insulin.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Glipizide: An oral hypoglycemic agent which is rapidly absorbed and completely metabolized.Pancreas, Artificial: Devices for simulating the activity of the pancreas. They can be either electromechanical, consisting of a glucose sensor, computer, and insulin pump or bioartificial, consisting of isolated islets of Langerhans in an artificial membrane.Body Mass Index: An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)Diabetic Nephropathies: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Pregnancy in Diabetics: The state of PREGNANCY in women with DIABETES MELLITUS. This does not include either symptomatic diabetes or GLUCOSE INTOLERANCE induced by pregnancy (DIABETES, GESTATIONAL) which resolves at the end of pregnancy.Hyperinsulinism: A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Diabetic Ketoacidosis: A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by KETOSIS; DEHYDRATION; and depressed consciousness leading to COMA.Insulin, Short-Acting: Insulin derivatives and preparations that are designed to induce a rapid HYPOGLYCEMIC EFFECT.Clinical Trials as Topic: Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.Monitoring, Physiologic: The continuous measurement of physiological processes, blood pressure, heart rate, renal output, reflexes, respiration, etc., in a patient or experimental animal; includes pharmacologic monitoring, the measurement of administered drugs or their metabolites in the blood, tissues, or urine.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Diabetic Retinopathy: Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Forced Expiratory Volume: Measure of the maximum amount of air that can be expelled in a given number of seconds during a FORCED VITAL CAPACITY determination . It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity.Biphasic Insulins: An insulin preparation that is designed to provide immediate and long term glycemic control in a single dosage. Biphasic insulin typically contains a mixture of REGULAR INSULIN or SHORT-ACTING INSULIN combined with a LONG-ACTING INSULIN.Incretins: Peptides which stimulate INSULIN release from the PANCREATIC BETA CELLS following oral nutrient ingestion, or postprandially.Diagnostic Equipment: Nonexpendable items used in examination.Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Critical Illness: A disease or state in which death is possible or imminent.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.TriglyceridesFatty Acids, Nonesterified: FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.Glycosuria: The appearance of an abnormally large amount of GLUCOSE in the urine, such as more than 500 mg/day in adults. It can be due to HYPERGLYCEMIA or genetic defects in renal reabsorption (RENAL GLYCOSURIA).Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Weight Loss: Decrease in existing BODY WEIGHT.Diet: Regular course of eating and drinking adopted by a person or animal.Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Insulin, Regular, Pork: Regular insulin preparations that contain the SUS SCROFA insulin peptide sequence.Glucose Intolerance: A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.Diabetic Neuropathies: Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)Gliclazide: An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion.Hyperglycemic Hyperosmolar Nonketotic Coma: A serious complication of TYPE 2 DIABETES MELLITUS. It is characterized by extreme HYPERGLYCEMIA; DEHYDRATION; serum hyperosmolarity; and depressed consciousness leading to COMA in the absence of KETOSIS and ACIDOSIS.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.Receptors, Glucagon: Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Injections, Subcutaneous: Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.Insulins: Peptide hormones that cause an increase in the absorption of GLUCOSE by cells within organs such as LIVER, MUSCLE and ADIPOSE TISSUE. During normal metabolism insulins are produced by the PANCREATIC BETA CELLS in response to increased GLUCOSE. Natural and chemically-modified forms of insulin are also used in the treatment of GLUCOSE METABOLISM DISORDERS such as DIABETES MELLITUS.Acarbose: An inhibitor of ALPHA-GLUCOSIDASES that retards the digestion and absorption of DIETARY CARBOHYDRATES in the SMALL INTESTINE.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Albuminuria: The presence of albumin in the urine, an indicator of KIDNEY DISEASES.Adamantane: A tricyclo bridged hydrocarbon.Allylamine: Possesses an unusual and selective cytotoxicity for VASCULAR SMOOTH MUSCLE cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Monitoring, Ambulatory: The use of electronic equipment to observe or record physiologic processes while the patient undergoes normal daily activities.Sodium-Glucose Transporter 2: A sodium-glucose transporter that is expressed in the luminal membrane of the PROXIMAL KIDNEY TUBULES.Epichlorohydrin: A chlorinated epoxy compound used as an industrial solvent. It is a strong skin irritant and carcinogen.Proinsulin: A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Eating: The consumption of edible substances.Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Insulin, Regular, Human: Regular insulin preparations that contain the HUMAN insulin peptide sequence.Disease Management: A broad approach to appropriate coordination of the entire disease treatment process that often involves shifting away from more expensive inpatient and acute care to areas such as preventive medicine, patient counseling and education, and outpatient care. This concept includes implications of appropriate versus inappropriate therapy on the overall cost and clinical outcome of a particular disease. (From Hosp Pharm 1995 Jul;30(7):596)Diet, Carbohydrate-Restricted: A diet that contains limited amounts of CARBOHYDRATES. This is in distinction to a regular DIET.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Adipocytes: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.Serum Albumin: A major protein in the BLOOD. It is important in maintaining the colloidal osmotic pressure and transporting large organic molecules.Streptozocin: An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Diet Therapy: By adjusting the quantity and quality of food intake to improve health status of an individual. This term does not include the methods of food intake (NUTRITIONAL SUPPORT).Rats, Zucker: Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene.Diabetes, Gestational: Diabetes mellitus induced by PREGNANCY but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (PREGNANCY IN DIABETICS). Gestational diabetes usually develops in late pregnancy when insulin antagonistic hormones peaks leading to INSULIN RESISTANCE; GLUCOSE INTOLERANCE; and HYPERGLYCEMIA.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Periodontal Prosthesis: Any restorative and replacement device that is used as a therapeutic aid in the treatment of periodontal disease. It is an adjunct to other forms of periodontal therapy and does not cure periodontal disease by itself. (Boucher's Clinical Dental Terminology, 3d ed)Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression.Patient Education as Topic: The teaching or training of patients concerning their own health needs.Infusions, Intravenous: The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.Weight Gain: Increase in BODY WEIGHT over existing weight.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Glucose Transporter Type 4: A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Islets of Langerhans Transplantation: The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.VermontPrediabetic State: The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).Kinetics: The rate dynamics in chemical or physical systems.Metabolic Syndrome X: A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.Body Composition: The relative amounts of various components in the body, such as percentage of body fat.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Perioperative Care: Interventions to provide care prior to, during, and immediately after surgery.Adiponectin: A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.PyrazinesFood: Any substances taken in by the body that provide nourishment.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Mice, Inbred C57BLMultivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time.United StatesGlycogenIntensive Care Units, Pediatric: Hospital units providing continuous surveillance and care to acutely ill infants and children. Neonates are excluded since INTENSIVE CARE UNITS, NEONATAL is available.Gastric Inhibitory Polypeptide: A gastrointestinal peptide hormone of about 43-amino acids. It is found to be a potent stimulator of INSULIN secretion and a relatively poor inhibitor of GASTRIC ACID secretion.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Adiposity: The amount of fat or lipid deposit at a site or an organ in the body, an indicator of body fat status.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Questionnaires: Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.ThiazolesMeals: A portion of the food eaten for the day, usually at regular occasions during the day.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Pancreas: A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.Bread: Baked food product made of flour or meal that is moistened, kneaded, and sometimes fermented. A major food since prehistoric times, it has been made in various forms using a variety of ingredients and methods.Mice, Obese: Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Exercise: Physical activity which is usually regular and done with the intention of improving or maintaining PHYSICAL FITNESS or HEALTH. Contrast with PHYSICAL EXERTION which is concerned largely with the physiologic and metabolic response to energy expenditure.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Chromans: Benzopyrans saturated in the 2 and 3 positions.
  • At 6 months, subjects receiving Symlin plus insulin achieved similar reductions in mean HbA1C levels, compared to subjects receiving placebo-plus-insulin (-0.47 +/- 0.07 % vs. -0.49 +/- 0.07 %, respectively), while using a significantly lower total and fast-acting insulin dose (-11.7%, -22.8% from baseline). (centerwatch.com)
  • Symlin was found to produce significantly superior improvements in reduction in HbA1c levels (-.57 %), placebo-subtracted HbA1c levels (-0.40 %), body weight (-1.5 kg), placebo-subtracted body weight (-1.7 kg), % change in rapid-acting insulin dose (-3.0 %), and % change in long-acting insulin dose (-0.2 %), at 6 months. (centerwatch.com)
  • At week 12, 110 study subjects achieved FBG ≤6.5 mmol/L, of whom 66 did not achieve HbA1c ≤7% and therefore initiated prandial insulin. (springer.com)
  • Measurement of HbA1c levels is the best method for medium-term to long-term diabetic control monitoring. (medscape.com)
  • To confirm the observed reduction in HbA1c for the 2.5 mg dose in EASE-3 by modelling and simulation analyses.Independent of data from EASE-3 that tested 2.5 mg, we simulated the effect of a 2.5 mg dose through patient-level, exposure-response modelling in the EASE-2 clinical study. (tripdatabase.com)
  • insulin dose adjustments made after treatment initiation that potentially limited HbA1c reductions. (tripdatabase.com)
  • The model was informed by pharmacokinetic, insulin dose , mean daily glucose and HbA1c data, and was verified by comparing the simulations with the observed HbA1c change in EASE-3. (tripdatabase.com)
  • 23 For form 2 diabetics with a poorly controlled HbA1c, the exercising program should begin steadily. (racernm.com)
  • This was an observational, cross-sectional study and involved assessment of HbA1c levels as a surrogate marker of the metabolic control in all patients seen during a regular four month interval at our outpatient clinic. (smw.ch)
  • The study compared the efficacy of Apidra(R) to insulin lispro in terms of change in glycohemoglobin (HBA1c), which is the amount of sugar bound to hemoglobin in the blood. (redorbit.com)
  • The change in HBA1c from baseline to endpoint for Apidra(R) and insulin lispro were similar. (redorbit.com)
  • Conclusions Both groups showed clinically relevant and long lasting decreases in HbA1c, rates of severe hypoglycaemia, and improved psychological measures, although few participants achieved glucose levels currently recommended by national and international guidelines. (bmj.com)
  • Treatment beyond lifestyle changes generally begins with oral antidiabetic agents, but these medicines only have transitory benefit, and the progressive nature of T2D requires therapeutic intensification to include insulin within 5 to 10 years for many patients ( 2 - 4 ). (sciencemag.org)
  • Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment. (lantus.com)
  • Previous works associated with insulin-based MN systems mainly focused on bolus insulin delivery without delaying or prolonging the dissolution or absorption of insulin ( 7 ). (sciencemag.org)
  • Nevertheless, the sustained or kinetically controlled delivery is more preferable than bolus insulin delivery and is essential to fulfill the full potential of transdermal delivery for maintaining drug concentrations within a therapeutic range over a predetermined period of time ( 8 ). (sciencemag.org)
  • Bolus insulin is produced during the digestion of meals. (wikipedia.org)