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Hyperbilirubinemia And Diabetes

Bilirubin As A New Biomarker Of Diabetes And Its Microvascular Complications

Bilirubin As A New Biomarker Of Diabetes And Its Microvascular Complications

Takeshi Nishimura*, Masami Tanaka, Risa Sekioka and Hiroshi Itoh Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan *Corresponding Author: Department of Internal Medicine, School of Medicine Keio University 35 Shinanomachi, Shinjuku-ku Tokyo 160-8582, Japan Tel: 81-3-5363-3797 Fax: 81-3-3359-2745 E-mail: [email protected] Citation: Nishimura T, Tanaka M, Sekioka R, Itoh H (2016) Bilirubin as a New Biomarker of Diabetes and its Microvascular Complications. Biochem Anal Biochem 5:245. doi:10.4172/2161-1009.1000245 Copyright: © 2016 Nishimura T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Biochemistry & Analytical Biochemistry Abstract Hyperglycemia is the hallmark of diabetes mellitus [DM]; it activates certain biochemical pathways leading to micro- and macrovascular complications in diabetic patients. Moreover, hyperglycemia generates oxidative stress and causes free radicalmediated lipid peroxidation. In turn, the oxidative stress causes endothelial dysfunction, and has been suggested as one of the important mechanisms underlying the onset and progression of diabetic vascular complications. Commentary Hyperglycemia is the hallmark of diabetes mellitus [DM]; it activates certain biochemical pathways leading to micro- and macrovascular complications in diabetic patients [1]. Moreover, hyperglycemia generates oxidative stress and causes free radicalmediated lipid peroxidation [2,3]. In turn, the oxidative stress causes endothelial dysfunction, and has been suggested as one of the important mechanisms un Continue reading >>

Gestational Diabetes And Your Baby's Health

Gestational Diabetes And Your Baby's Health

Insulin, a hormone produced by your pancreas, is necessary to move glucose (or sugar) into your cells after your body breaks down food for energy. During pregnancy, your body becomes less sensitive to the effects of insulin, which can lead to what’s known as gestational diabetes. If you have gestational diabetes, your blood sugar can become too high, creating a number of health risks for your baby. Gestational Diabetes and Your Baby's Health If your blood sugar remains consistently elevated during pregnancy, the excess sugar can pass through your womb to your unborn baby. This can increase your child’s future risk of obesity and type 2 diabetes. Other health risks associated with gestational diabetes include: Macrosomia. This term simply means "big baby" and applies to any baby whose birth weight is above 8 pounds, 13 ounces. A baby with macrosomia can experience difficulties during the childbirth process. The most common problem that big babies encounter is damage to the nerves and muscles in their shoulders during vaginal delivery. Your doctor will monitor the size of your baby by performing ultrasound exams throughout your pregnancy. If your doctor is concerned about the size of your baby, a Caesarean section may be recommended. Hypoglycemia. If your unborn baby is exposed to high blood sugar levels while in the womb, the baby will eventually make extra insulin on its own to deal with the excess sugar. This surge in insulin can cause the baby's glucose to drop sharply right after birth, a condition called "hypoglycemia." Low blood sugar is dangerous because your baby depends almost exclusively on glucose for energy at the time of birth. Signs and symptoms of hypoglycemia include seizures, sluggishness, and difficulty breathing. For this reason, doctors will check Continue reading >>

A Pilot Study Of Moderate Hyperbilirubinemia In Type 1 Diabetes Mellitus

A Pilot Study Of Moderate Hyperbilirubinemia In Type 1 Diabetes Mellitus

You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. A Pilot Study of Moderate Hyperbilirubinemia in Type 1 Diabetes Mellitus The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT01421355 Information provided by (Responsible Party): Mark Alan Creager, MD, Brigham and Women's Hospital Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Specific Aim: To establish the feasibility of studying the change in endothelial function caused by induced moderate hyperbilirubinemia in type 1 diabetes. Atazanavir, a drug that inhibits bilirubin conjugation, will be used to induce moderate hyperbilirubinemia. Endothelial function will be measured before and after atazanavir therapy. In addition, plasma markers of antioxidant capacity and oxidant stress will be measured as proof-of-concept that induced moderate hyperbilirubinemia has favorable effects on oxidative stress in type 1 diabetes. Diabetes mellitus (DM) is associated with a markedly increased risk of both macro- and microvascular disease. Excess pro-oxidants and insufficient antioxidants each contributes to oxidant stress in DM. Oxidant stress induces endothelial dysfunction, a major determinant of vascular damage. In DM, hyperglycemia and elevated free fatty acids (FFAs) induce generation of reactive oxygen species (ROS) by stimulating protein kinase C (PKC) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Figure 1). In addition, hyperglycemia activates the renin-an Continue reading >>

Infant Of Diabetic Mother

Infant Of Diabetic Mother

Women may have diabetes during pregnancy in 2 ways: Gestational diabetes is high blood sugar (diabetes) that starts or is first diagnosed during pregnancy. If the diabetes is not well controlled during pregnancy, the baby is exposed to high blood sugar levels. This can affect the baby and mom during the pregnancy, at the time of birth, and after birth. Infants who are born to mothers with diabetes are often larger than other babies. Larger infants make vaginal birth harder. This can increase the risk for nerve injuries and other trauma during birth. Also, C-sections are more likely. The infant is more likely to have periods of low blood sugar (hypoglycemia) shortly after birth, and during first few days of life. Mothers with poorly controlled diabetes are also more likely to have a miscarriage or stillborn child. If the mother had diabetes before her pregnancy, her infant has an increased risk of birth defects if the disease was not well controlled. Continue reading >>

Liver Disease And Diabetes Mellitus

Liver Disease And Diabetes Mellitus

CLINICAL DIABETES VOL. 17 NO. 2 1999 These pages are best viewed with Netscape version 3.0 or higher or Internet Explorer version 3.0 or higher. When viewed with other browsers, some characters or attributes may not be rendered correctly. FEATURE ARTICLE Gavin N. Levinthal, MD, and Anthony S. Tavill, MD, FRCP, FACP IN BRIEF Liver disease may cause or contribute to, be coincident with, or occur as a result of diabetes mellitus. This article addresses these associations. This article addresses the role of the liver in normal glucose homeostasis and discusses a variety of liver conditions associated with abnormal glucose homeostasis. This association may explain the pathogenesis of the liver disease or of the abnormal glucose homeostasis, or may be purely coincidental (Table 1). Table 1. Liver Disease and Diabetes Mellitus 1. Liver disease occurring as a consequence of diabetes mellitus Glycogen deposition Steatosis and nonalcoholic steatohepatitis (NASH) Fibrosis and cirrhosis Biliary disease, cholelithiasis, cholecystitis Complications of therapy of diabetes (cholestatic and necroinflammatory) 2 . Diabetes mellitus and abnormalities of glucose homeostasis occurring as a complication of liver disease Hepatitis Cirrhosis Hepatocellular carcinoma Fulminant hepatic failure Postorthotopic liver transplantation 3 . Liver disease occurring coincidentally with diabetes mellitus and abnormalities of glucose homeostasis Hemochromatosis Glycogen storage diseases Autoimmunebiliary disease The prevalence of type 1 diabetes in the United States is ~0.26%. The prevalence of type 2 diabetes is far higher, ~1–2% in Caucasian Americans and up to 40% in Pima Indians. According to the Centers for Disease Control and Prevention, hepatitis C alone chronically infects more than 1.8% of the A Continue reading >>

Neonatal Hyperbilirubinemia

Neonatal Hyperbilirubinemia

Among healthy term infants, the threshold typically is considered to be a level > 18 mg/dL (> 308 mol/L); see Figure: Risk of hyperbilirubinemia in neonates 35 wk gestation. . However, infants who are premature , small for gestational age , and/or ill (eg, with sepsis , hypothermia , or hypoxia) are at much greater risk. In such infants, although risk increases with increasing hyperbilirubinemia, there is no level of hyperbilirubinemia that is considered safe; treatment is given based on age and clinical factors. There are now suggested operational thresholds to initiate phototherapy based on gestational age. Neurotoxicity is the major consequence of neonatal hyperbilirubinemia. An acute encephalopathy can be followed by a variety of neurologic impairments, including cerebral palsy and sensorimotor deficits; cognition is usually spared. Kernicterus is the most severe form of neurotoxicity. Although it is now rare, kernicterus still occurs and can nearly always be prevented. Kernicterus is brain damage caused by unconjugated bilirubin deposition in basal ganglia and brain stem nuclei, caused by either acute or chronic hyperbilirubinemia. Normally, bilirubin bound to serum albumin stays in the intravascular space. However, bilirubin can cross the blood-brain barrier and cause kernicterus in certain situations: When serum bilirubin concentration is markedly elevated When serum albumin concentration is markedly low (eg, in preterm infants) When bilirubin is displaced from albumin by competitive binders Competitive binders include drugs (eg, sulfisoxazole, ceftriaxone, aspirin) and free fatty acids and hydrogen ions (eg, in fasting, septic, or acidotic infants). Risk of hyperbilirubinemia in neonates 35 wk gestation. Risk is based on total serum bilirubin levels. (Adapted f Continue reading >>

Simultaneous Hypoprothrombinemia, Indirect Hyperbilirubinemia, And Diabetes Mellitus

Simultaneous Hypoprothrombinemia, Indirect Hyperbilirubinemia, And Diabetes Mellitus

, Volume 8, Issue6 , pp 492498 | Cite as Simultaneous hypoprothrombinemia, indirect hyperbilirubinemia, and diabetes mellitus A case of simultaneous hypoprothrombinemia, hyperbilirubinemia, and diabetes mellitus is presented. The findings suggest an interrelationship of these constitutional defects in the liver cell. It is our impression that the nature of these defects favors a congenital etiology. Public HealthDiabetes MellitusLiver CellCongenital EtiologyConstitutional Defect These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. The authors gratefully acknowledge the advice and encouragement of Dr. Richard Nagler, Fitzsimons General Hospital, and thank Drs. Kurt Von Kaulla and Fred Kern of the University of Colorado School of Medicine for reviewing the manuscript. This is a preview of subscription content, log in to check access. Unable to display preview. Download preview PDF. Quick, A. J. Hereditary bleeding diseases.J.A.M.A. 178:941, 1961. PubMed Google Scholar Foulk, William T.et al. Constitutional hepatic dysfunction (Gilbert's Disease): Natural history and related syndromes.Medicine35:25, 1959. Google Scholar Meyer, E. L. Function of liver in diabetes mellitus.Arch. Inter. Med. 47:182, 1931. Google Scholar Rabinowitch, I. M. Diabetes mellitus.Am. J. Digest. Dis. 16:95, 1949. Google Scholar Portis, Sidney A.Diseases of the Digestive System, Lea, Philadelphia, Pa., 1953, p. 1030. Google Scholar Quick, A. J. The diagnosis of common hereditary hemorrhagic diseases.Ann. Int. Med. 55(2):201, 1961. PubMed Google Scholar Borchgerevink, C. F.et al. A study of a case of congenital hypoprothrombinemia.Brit. J. Haemat.5:294, 1959. PubMed Google Scholar Barnhart, M. I. C Continue reading >>

The Role Of Bilirubin In Diabetes, Metabolic Syndrome, And Cardiovascular Diseases

The Role Of Bilirubin In Diabetes, Metabolic Syndrome, And Cardiovascular Diseases

The Role of Bilirubin in Diabetes, Metabolic Syndrome, and Cardiovascular Diseases We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. The Role of Bilirubin in Diabetes, Metabolic Syndrome, and Cardiovascular Diseases Bilirubin belongs to a phylogenetically old superfamily of tetrapyrrolic compounds, which have multiple biological functions. Although for decades bilirubin was believed to be only a waste product of the heme catabolic pathway at best, and a potentially toxic compound at worst; recent data has convincingly demonstrated that mildly elevated serum bilirubin levels are strongly associated with a lower prevalence of oxidative stress-mediated diseases. Indeed, serum bilirubin has been consistently shown to be negatively correlated to cardiovascular diseases (CVD), as well as to CVD-related diseases and risk factors such as arterial hypertension, diabetes mellitus, metabolic syndrome, and obesity. In addition, the clinical data are strongly supported by evidence arising from both in vitro and in vivo experimental studies. This data not only shows the protective effects of bilirubin per se; but additionally, of other products of the heme catabolic pathway such as biliverdin and carbon monoxide, as well as its key enzymes (heme oxygenase and biliverdin reductase); thus, further underlining the biological impacts of this pathway. In this review, detailed information on the experimental and clinical evidence between the heme cat Continue reading >>

Gestational Diabetes

Gestational Diabetes

What is gestational diabetes? Gestational diabetes is a condition marked by high blood glucose (sugar) levels that are discovered during pregnancy. It is defined as carbohydrate intolerance. About two to 10 percent of all pregnant women in the U.S. are diagnosed with gestational diabetes. Am I at risk for gestational diabetes? These factors increase your risk of developing diabetes during pregnancy: Being overweight before becoming pregnant (if you are 20% or more over your ideal body weight) Family history of diabetes (if your parents or siblings have diabetes) Being over age 25 Previously giving birth to a baby that weighed more than 9 pounds Previously giving birth to a stillborn baby Having gestational diabetes with an earlier pregnancy Being diagnosed with pre-diabetes Having polycystic ovary syndrome Being African-American, Hispanic/Latino, Asian-American, American Indian, or Pacific Islander American Keep in mind that half of women who develop gestational diabetes have no known risk factors. What causes gestational diabetes? Gestational diabetes is caused by some hormonal changes that occur in all women during pregnancy. The placenta is the organ that connects the baby (by the umbilical cord) to the uterus and transfers nutrients from the mother to the baby. Increased levels of certain hormones made in the placenta can prevent insulin—a hormone that controls blood sugar—from managing glucose properly. This condition is called "insulin resistance." As the placenta grows larger during pregnancy, it produces more hormones and increases this insulin resistance. Usually, the mother’s pancreas is able to produce more insulin (about three times the normal amount) to overcome the insulin resistance. If it cannot, sugar levels will rise, resulting in gestational dia Continue reading >>

Hyperbilirubinemia In Infants Of Diabetic Mothers.

Hyperbilirubinemia In Infants Of Diabetic Mothers.

Abstract Large for gestational age (LGA) infants of insulin-dependent diabetic mothers (IDM), appropriate for gestational age (AGA) IDM, and infants of nondiabetic mothers were compared for the incidence of neonatal hyperbilirubinemia and related etiologic factors. At 60 hours of age, LGA IDM had significantly higher serum bilirubin concentrations (12.3 +/- 2.1 mg/100 ml) than AGA IDM (7.6 +/- 3.9 mg/100 ml) or control infants (7.8 +/- 2.8 mg/100 ml) (P < .001). Peak serum bilirubin concentrations were also significantly higher in LGA IDM (14.4 +/- 2.1 mg/100 ml) than in AGA IDM (8.4 +/- 3.7 mg/100ml) or control infants (8.6 +/- 3.3 mg/100 ml) (P < .001). Mean percent of carboxyhemoglobin was used as an indicator of hemolysis and showed a significant elevation in LGA IDM (1.51 +/- 0.19) when compared to AGA IDM (1.10 +/- 0.27) and control infants (1.19 +/- 0.33) (P < .05). No significant differences were found among the three groups with respect to mode of delivery, frequency of pitocin administration, 5-minute Apgar scores, incidence of isoimmunization, incidence of enclosed hemorrhage, hemoglobin concentration, bilirubin concentrations at 12 hours, and percent of weight loss. Our data suggest that only LGA IDM are at increased risk for hyperbilirubinemia and that increased heme turnover is a significant factor in the pathogenesis. Continue reading >>

Infant Of A Diabetic Mother

Infant Of A Diabetic Mother

INTRODUCTION Diabetes in pregnancy is associated with an increased risk of fetal, neonatal, and long-term complications in the offspring. Maternal diabetes may be pregestational (ie, type 1 or type 2 diabetes diagnosed before pregnancy with a prevalence rate of about 1.8 percent) or gestational (ie, diabetes diagnosed during pregnancy with a prevalence rate of about 7.5 percent). The outcome is generally related to the onset and duration of glucose intolerance during pregnancy and severity of the mother's diabetes. (See "Pregestational diabetes: Preconception counseling, evaluation, and management".) This topic will review the complications seen in the offspring of mothers with diabetes and the management of affected neonates. The prenatal management of pregestational and gestational diabetic mothers is discussed in separate topic reviews. (See "Diabetes mellitus in pregnancy: Screening and diagnosis" and "Pregestational diabetes mellitus: Obstetrical issues and management" and "Gestational diabetes mellitus: Obstetrical issues and management" and "Gestational diabetes mellitus: Glycemic control and maternal prognosis" and "Pregestational diabetes: Preconception counseling, evaluation, and management".) FETAL EFFECTS Poor glycemic control in pregnant diabetic women leads to deleterious fetal effects throughout pregnancy, as follows [1]: In the first trimester and time of conception, maternal hyperglycemia can cause diabetic embryopathy resulting in major birth defects and spontaneous abortions. This primarily occurs in pregnancies with pregestational diabetes. The risk for congenital malformations is only slightly increased with gestational diabetes mellitus (GDM) compared with the general population (odds ratio [OR] 1.1-1.3). The risk of malformations increases as mate Continue reading >>

Gestational Diabetes In Primary Care

Gestational Diabetes In Primary Care

In many cases, the physician who provides prenatal care will become the baby's caregiver as well. As such, the neonatal complications of GDM are important to consider. The potential sequelae of shoulder dystocia are Erb's palsy, a stretch injury to the brachial plexus, and intrapartum fetal hypoxia, with the possibility of a hypoxic ischemic event or death if the hypoxia is extreme or prolonged. The flaccid paralysis of Erb's palsy usually resolves in the first few days to weeks but occasionally is lifelong. Other neonatal complications of GDM are hypoglycemia, polycythemia, and respiratory distress. Secondary to fetal hyperinsulinemia, hypoglycemia is defined as a heel-stick blood sugar < 35 mg/dL in a full-term neonate and < 25 mg/dL in one born preterm. The hypoglycemia typically resolves with feeding of either milk or a glucose solution. If the baby is symptomatic or the hypoglycemia profound, an IV bolus of 10% dextrose is recommended -- 0.25 mg/kg followed by 4-6 mg glucose/kg/min with gradual titration. Blood sugar monitoring is continued every hour until it has stabilized. Polycythemia is a result of chronic intrauterine hypoxemia and placental insufficiency secondary to poor glycemic control. Hypoxemia causes increased fetal erythropoietin release and subsequent polycythemia.[ 52 ] When these extra red blood cells break down, there is increased incidence of hyperbilirubinemia at days to weeks after birth. Respiratory distress is the most serious complication for the neonate. Fetuses affected by GDM are at elevated risk (perhaps 5- to 6-fold greater) of lung immaturity compared with age-matched controls.[ 53 ] Oxygen supplementation, ventilatory support, and surfactant replacement are among the treatments available, and care may require consultation with a neon Continue reading >>

Hyperbilirubinemia In Infants Of Diabetic Mothers

Hyperbilirubinemia In Infants Of Diabetic Mothers

Hyperbilirubinémie chez les enfants nouveau-nés de mères diabétiques Taylor P.M. · Wolfson J.H. · Bright N.H. · Birchard E.L. · Derinoz M.N. · Watson D.W. Authors’ addresses: Paul M. Taylor, M.D., Jerome H. Wolfson, M.D., and Doris W. Watson, B.S., Elizabeth Steel Magee Hospital, Pittsburgh 13, Pa. (USA), Nancy H. Bright, M.D., 216 Metz Avenue, Akron 3, Ohio (USA), Edna L. Birchard, M.D., Medical Arts Building, Hamilton, Ontario (Canada), and Mahmut N. Derinoz, M.D., Resatbey Mahallesi Sokak-112, No. 1, Adana (Turkey) Continue reading >>

Jaundice In Newborns Associated With Type 1 Diabetes

Jaundice In Newborns Associated With Type 1 Diabetes

Nov. 11, 1999 (Los Angeles) -- It is not unusual for a child in the womb to develop blood proteins that are incompatible with the corresponding proteins in its mother's blood. Often these infants are born with jaundice, a yellowish discoloration of the skin due to an abnormal breakdown of blood products. A new study has found an association between this form of jaundice in newborns and a higher occurrence of diabetes that starts in childhood, also known as type 1 diabetes. However, "we are nowhere near saying that if you have a particular [type of blood protein], your risk is increased," one of the investigators tells WebMD. In the paper, published in the October issue of the journal Diabetes Care, lead researcher Gisela G. Dahlquist, MD, PhD, of Umeå University Hospital in Sweden, and co-authors from Ireland and Hungary, found a strong association between jaundice caused by incompatibility of the ABO blood protein between mother and infant and the child's subsequent risk of developing type 1 diabetes. ABO blood proteins determine the type of blood the child will have, such as A, B, or O. Certain situations can arise where the blood type of the child will cause a reaction or be incompatible with the mother's blood type, and thus cause problems. If a severe reaction develops, the child may die. Incompatibility to Rh factor, another blood protein, had no effect. The Rh factor determines whether your blood type is positive or negative, as in B+ or O-. Other important diabetes risk factors included a mother older than 25, a high blood pressure disorder during pregnancy known as preeclampsia, and lung disease in the newborn. The authors looked at approximately 900 cases of children who developed diabetes before age 15 from seven countries throughout Europe, and compared the Continue reading >>

Effect Of Bilirubin Concentration On The Risk Of Diabetic Complications: A Meta-analysis Of Epidemiologic Studies

Effect Of Bilirubin Concentration On The Risk Of Diabetic Complications: A Meta-analysis Of Epidemiologic Studies

Effect of bilirubin concentration on the risk of diabetic complications: A meta-analysis of epidemiologic studies Scientific Reports volume 7, Articlenumber:41681 (2017) Diabetes can affect many parts of the body and is associated with serious complications. Oxidative stress is a major contributor in the pathogenesis of diabetic complications and bilirubin has been shown to have antioxidant effects. The number of studies on the effect of bilirubin on the risk of diabetic complications has increased, but the results are inconsistent. Thus, we performed a meta-analysis to determine the relationship between bilirubin concentration and the risk of diabetic complications, and to investigate if there was a dose-response relationship. We carried out an extensive search in multiple databases. A fixed or random-effects model was used to calculate the pooled estimates. We conducted a dose-response meta-analysis to analyze the association between these estimates. A total of 132,240 subjects from 27 included studies were analyzed in our meta-analysis. A negative nonlinear association between bilirubin concentration and the risk of diabetic complications was identified (OR: 0.77, 95% CI: 0.730.81), with a nonlinear association. We also found that there was a negative association between bilirubin concentration and the risk of diabetic nephropathy, diabetic retinopathy and diabetic neuropathy. The results of our meta-analysis indicate that bilirubin may play a protective role in the occurrence of diabetic complications. Diabetes Mellitus (DM) is an important non-communicable disease, and is a serious threat to human health and global economies. Due to population ageing, urbanization and lifestyle changes, the number of people with DM has increased sharply in both developed and devel Continue reading >>

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