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.
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.
Diabetes Mellitus, Experimental
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.
Substances which lower blood glucose levels.
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).
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.
Abnormally high BLOOD GLUCOSE level.
Glucose Tolerance Test
VASCULAR DISEASES that are associated with DIABETES MELLITUS.
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.
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)
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.
The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.
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).
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.
Pregnancy in Diabetics
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)
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.
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.
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.
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.
A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.
A disease that is characterized by frequent urination, excretion of large amounts of dilute URINE, and excessive THIRST. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or VASOPRESSIN) secreted by the NEUROHYPOPHYSIS, impaired KIDNEY response to ADH, and impaired hypothalamic regulation of thirst.
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)
The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.
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.
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.
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.
The presence of albumin in the urine, an indicator of KIDNEY DISEASES.
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.
A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 126.96.36.199.
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.
The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.
Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.
Mice, Inbred NOD
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)
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.
Rats, Inbred BB
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).
Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances.
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.
Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.
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)
Dipeptidyl-Peptidase IV Inhibitors
Coronary Artery Disease
Common foot problems in persons with DIABETES MELLITUS, caused by any combination of factors such as DIABETIC NEUROPATHIES; PERIPHERAL VASCULAR DISEASES; and INFECTION. With the loss of sensation and poor circulation, injuries and infections often lead to severe foot ulceration, GANGRENE and AMPUTATION.
The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.
Genetic Predisposition to Disease
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.
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.
Conditions with excess LIPIDS in the blood.
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.
Predictive Value of Tests
In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.
Proportional Hazards Models
Asian Continental Ancestry Group
Kidney Failure, Chronic
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.
Glucose Clamp Technique
A distribution in which a variable is distributed like the sum of the squares of any given independent random variable, each of which has a normal distribution with mean of zero and variance of one. The chi-square test is a statistical test based on comparison of a test statistic to a chi-square distribution. The oldest of these tests are used to detect whether two or more population distributions differ from one another.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Islet Amyloid Polypeptide
A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.
Indians, North American
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
Islets of Langerhans Transplantation
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)
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.
Analysis of Variance
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)
A hereditary condition characterized by multiple symptoms including those of DIABETES INSIPIDUS; DIABETES MELLITUS; OPTIC ATROPHY; and DEAFNESS. This syndrome is also known as DIDMOAD (first letter of each word) and is usually associated with VASOPRESSIN deficiency. It is caused by mutations in gene WFS1 encoding wolframin, a 100-kDa transmembrane protein.
Disease Models, Animal
Severity of Illness Index
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.
Peptides which stimulate INSULIN release from the PANCREATIC BETA CELLS following oral nutrient ingestion, or postprandially.
Glomerular Filtration Rate
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.
Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.
Diabetes Mellitus, Lipoatrophic
Polymorphism, Single Nucleotide
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)
Age of Onset
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Glycosylation End Products, Advanced
Products derived from the nonenzymatic reaction of GLUCOSE and PROTEINS in vivo that exhibit a yellow-brown pigmentation and an ability to participate in protein-protein cross-linking. These substances are involved in biological processes relating to protein turnover and it is believed that their excessive accumulation contributes to the chronic complications of DIABETES MELLITUS.
Diabetes complications in which VENTRICULAR REMODELING in the absence of CORONARY ATHEROSCLEROSIS and hypertension results in cardiac dysfunctions, typically LEFT VENTRICULAR DYSFUNCTION. The changes also result in myocardial hypertrophy, myocardial necrosis and fibrosis, and collagen deposition due to impaired glucose tolerance.
Drug Therapy, Combination
The transference of a pancreas from one human or animal to another.
Decrease in existing BODY WEIGHT.
Rats, Inbred OLETF
Transmembrane proteins that form the beta subunits of the HLA-DQ antigens.
A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)
African Continental Ancestry Group
Autonomic Nervous System Diseases
Diseases of the parasympathetic or sympathetic divisions of the AUTONOMIC NERVOUS SYSTEM; which has components located in the CENTRAL NERVOUS SYSTEM and PERIPHERAL NERVOUS SYSTEM. Autonomic dysfunction may be associated with HYPOTHALAMIC DISEASES; BRAIN STEM disorders; SPINAL CORD DISEASES; and PERIPHERAL NERVOUS SYSTEM DISEASES. Manifestations include impairments of vegetative functions including the maintenance of BLOOD PRESSURE; HEART RATE; pupil function; SWEATING; REPRODUCTIVE AND URINARY PHYSIOLOGY; and DIGESTION.
A condition of fetal overgrowth leading to a large-for-gestational-age FETUS. It is defined as BIRTH WEIGHT greater than 4,000 grams or above the 90th percentile for population and sex-specific growth curves. It is commonly seen in GESTATIONAL DIABETES; PROLONGED PREGNANCY; and pregnancies complicated by pre-existing diabetes mellitus.
Transcription Factor 7-Like 2 Protein
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.
An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion.
Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed)
Randomized Controlled Trials as Topic
A parliamentary democracy with a constitutional monarch in southeast Asia, consisting of 11 states (West Malaysia) on the Malay Peninsula and two states (East Malaysia) on the island of BORNEO. It is also called the Federation of Malaysia. Its capital is Kuala Lumpur. Before 1963 it was the Union of Malaya. It reorganized in 1948 as the Federation of Malaya, becoming independent from British Malaya in 1957 and becoming Malaysia in 1963 as a federation of Malaya, Sabah, Sarawak, and Singapore (which seceded in 1965). The form Malay- probably derives from the Tamil malay, mountain, with reference to its geography. (From Webster's New Geographical Dictionary, 1988, p715 & Room, Brewer's Dictionary of Names, 1992, p329)
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
Antibodies specific to INSULIN.
The transference of a kidney from one human or animal to another.
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.
Primary Health Care
Practice Guidelines as Topic
Directions or principles presenting current or future rules of policy for assisting health care practitioners in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery.
Increase in BODY WEIGHT over existing weight.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
Country located in EUROPE. It is bordered by the NORTH SEA, BELGIUM, and GERMANY. Constituent areas are Aruba, Curacao, Sint Maarten, formerly included in the NETHERLANDS ANTILLES.
Receptor-Like Protein Tyrosine Phosphatases, Class 8
Fatty Acids, Nonesterified
Pathological processes of the KIDNEY or its component tissues.
Protein Tyrosine Phosphatase, Non-Receptor Type 1
A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.
A sulfonylurea hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. (From Martindale, The Extra Pharmacopoeia, 30th ed, p277)
Sodium-Glucose Transporter 2
A sodium-glucose transporter that is expressed in the luminal membrane of the PROXIMAL KIDNEY TUBULES.