Clinical Chemistry Carbohydrates PDF

lOMoARcPSD|29614747 [Clinical Chemistry] Carbohydrates Computer Engineering (Far Eastern University) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Caila Mae Dacquel ([email protected]) ...

lOMoARcPSD|29614747 [Clinical Chemistry] Carbohydrates Computer Engineering (Far Eastern University) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Caila Mae Dacquel ([email protected])  lOMoARcPSD|29614747 CLINICAL CHEMISTRY Carbohydrates OUTLINE By the number of sugar units I. Carbohydrates III. Hyperglycemia o Hydrolysis a. General Description a. Diabetes mellitus o chaining of sugars relies on the formation of glycoside bonds b. Classifications IV. Hypoglycemia that are bridges of oxygen atoms c. Functions V. Genetic Defects in Metabolism o when two carbohydrate molecules join, a water molecule is d. Chemical Properties VI. Carbohydrate Analysis produced e. Metabolism a. Specimen Considerations o when they split, one molecule of water is used to form the II. Glucose b. Glucose Determination Method individual compounds a. General Description c. Interpretation of Results o glycoside linkages of carbohydrate can involve any number b. Metabolism of carbons (certain carbons are favored, depending on (Fate, Pathways, and carbohydrate) Regulation)  simple sugars  cannot be hydrolyzed to simpler form CARBOHDYRATES  contain 3, 4, 5,and 6 or more carbon atoms ❖ compounds containing C, H, and O  most common forms: ❖ All contain carbonyl (C=O) and hydroxyl (-OH) functional groups ★ glucose - D-glucose (principal in the ❖ Formula: Cx(H2O)y Monosaccharides plasma and the only monosaccharide ❖ carbohydrate derivatives can be formed by the addition of other that can be directly utilized by the cells chemical groups as a source of energy.  phosphates ★ fructose  sulfates ★ galactose  amines  formed when two monosaccharide units are joined by a glycosidic linkage ❖ Classifications:  on hydrolysis, disaccharides will be split into By the number of carbons two monosaccharides by disaccharide o Triose - three carbons (E.g., glyceraldehyde – smallest) enzymes (e.g. lactase) = located on the o Tetrose - four carbons microvilli of the intestine o Pentose - five carbons Disaccharides  most common form: o Hexose - six carbons ★ maltose = 1 →4 linkage (glucose + glucose) By the location of the C=O function group ★ lactose – milk sugar (glucose + galactose) ★ o hydrate of aldehyde or ketone derivatives based on the location of sucrose – table sugar (glucose + the C=O functional group fructose) o 2 forms: Oligosaccharides  chaining of 3 to 10 sugar units terminal carbonyl group (O=CH-) aldehyde  linkage of many monosaccharide units Aldose  on hydrolysis, this will yield more than 10 monosaccharides  amylase - hydrolyzes starch to middle carbonyl group (O=C) disaccharides in the duodenum ketone  most common form: Ketose Polysaccharides ★ starch (glucose molecules) ★ glycogen – major storage form of glucose in man and majorly stored in o Models: the liver (85%) and skeletal muscles o Fisher projection (15%)  aldehyde or ketone group at the top ★ cellulose – plants  carbons numbered starting at the aldehyde or ★ chitin - fungi ketone end  compound can be represented as a straight chain or By the stereochemistry of the compound show a representation of cyclic, hemiacetal form o central carbons of a carbohydrate are asymmetric (chiral) = four different groups are attached to the carbon atoms o chiral carbon allows for various spatial arrangements around each stereogenic centers (forming stereoisomers) o Stereoisomers o have the same order and types of bonds but different spatial arrangements and different properties o for each asymmetric carbon, there are 2n possible isomers o Haworth projection o monosaccharide is assigned to the D or L series according to the  compound in the cyclic form that is more configuration at the highest numbered asymmetric carbon representative of the actual structure o if the hydroxyl group projects to  formed when the functional (carbonyl) group reacts the right in the Fisher projection with an alcohol group on the same sugar o receives the prefix D-  ketone = hemiketal ring o most sugars in humans are in D series  aldehyde = hemiacetal ring this form Downloaded by Caila Mae Dacquel ([email protected])  lOMoARcPSD|29614747 CLINICAL CHEMISTRY Carbohydrates o if the hydroxyl group projects to Pancreatic and salivary amylases the left in the Fisher projection o converts nonabsorbable polysaccharides into o receives the prefix L- disaccharides and dextrins L series Maltase, sucrase, lactase o converts maltose, sucrose and lactose into monosaccharides. o happens in the microvilli of small intestines o inherited deficiencies of lactase predispose an individual NOTE: These stereoisomers (enantiomers) are images that cannot be overlapped to lactose intolerance and are nonsuperimposable GLUCOSE ❖ primary source of energy for humans ❖ Functions:  brain is completely dependent on glucose for energy  Energy source production  Component of nucleic acids – ribose and deoxyribose  2/3rd of glucose utilization in resting adults occurs on the CNS  Modification of proteins through glycosylation ❖ enter red blood cells the cell freely o Glycemic control is important in diabetes because  skeletal muscle and adipose tissues: can only enter with the hyperglycemia leads to development and progression of help of insulin by stimulating the expression of glucose microvascular (nephropathy, retinopathy, neuropathy) and transporter 4 macrovascular (atherosclerosis 2-4x) complications o Polysaccharides and disaccharides are non-absorbable  Nervous system (including brain) depends on glucose from the polymers which must be converted first into extracellular fluid (ECF) for energy monosaccharides before being absorbed in the small  nervous tissue cannot concentrate or store carbohydrates = it intestines. is critical to maintain a steady supply of glucose to the tissue o Intermediate products of glucose metabolism: pyruvic acid,  concentration of glucose in the ECF must be maintained in a lactic acid and acetylcoenzyme A narrow range o End products of glucose metabolism: carbon dioxide, water  when the concentration falls below a certain level = nervous and ATP tissue loses the primary energy source and is incapable of maintaining normal function ❖ Chemical Properties: REDUCING SUBSTANCES some carbohydrates can reduce other compounds ❖ o Metabolism: FATE OF GLUCOSE o carbohydrate must contain a ketone or an aldehyde group to be a  Most of our ingested carbohydrates are polymers or reducing substance polysaccharides (e.g. starch and glycogen). o carbohydrates can form glycosidic bonds with other carbohydrates Mouth and with noncarbohydrates o Salivary amylase – converts ingested polysaccharides o two sugar molecules can be joined in tandem forming a glycosidic (starch) into disaccharides and dextrins bond between the hemiacetal group and the hydroxyl group Pancreas o in forming the glycosidic bond, an acetal is generated on one sugar o Pancreatic amylase - responsible for the further (at carbon 1) in place of the hemiacetal catabolism or digestion of disaccharides and dextrins o if the bond forms with one of the other carbons on the Intestinal mucosa carbohydrate other than the anomeric (reducing) carbon, the o Lactase, Sucrase, Maltase – gut-derived enzymes that anomeric carbon is unaltered and the resulting compound convert nonabsorbable polymers into absorbable remains a reducing substance monosaccharides o Examples of reducing substances:  Sucrase →sucrose to glucose and fructose o glucose  Lactase → lactose to glucose and galactose o maltose o fructose NOTE: NO carbohydrate degradation happens in the stomach since o lactose salivary amylase is inactivated by the gastric juice (pH 1-3 due to o galactose HCl content).  all monosaccharides and many disaccharides are reducing agents  Absorbed monosaccharides (glucose, fructose, galactose) because a free aldehyde or ketone (the open-chain form) can be migrate to the liver via the hepatic portal vein and enters the oxidized under the proper conditions bloodstream causing post-prandial hyperglycemia.  dissacharide remains a reducing agent when the hemiacetal or o Glucose - only carbohydrate to be directly used for ketal hydroxyl group is not linked to another molecule, both energy or stored as glycogen maltose and lactose are reducing agents, whereas sucrose is not o Galactose and fructose - converted to glucose before  Nonreducing substances: they can be used o resulting compound is no longer a reducing substance if the bond is formed with the anomeric carbon on the other  After glucose enters the cell, it is quickly shunted into one of carbohydrate three possible metabolic pathways (depending on the o do not have an active ketone or aldehyde group availability of substrates or the nutritional status of the cell) o they will not reduce other compounds  Ultimate goal of the cell: convert glucose to carbon dioxide and o sucrose (table sugar) = most common nonreducing sugar water  Cell requires oxygen for the final steps in the electron transport ❖ Metabolism: chain (ETC)  liver, pancreas, and other endocrine glands are all involved in  Nicotinamide adenine dinucleotide (NAD): reduced form (NADH) controlling the blood glucose concentrations within a narrow range act as an intermediate to couple glucose oxidation to the ETC in  during a brief fast, glucose is supplied to the ECF from the liver the mitochondria where much of the ATP is gained through glycogenolysis  Pancreatic beta cells senses hyperglycemia and secretes  fasting period > 1 day = glucose is synthesized from other sources insulin through gluconeogenesis  Insulin-mediated activities: glycolysis, glycogenesis and  ENZYMES RESPONSIBLE IN METABOLISM: lipogenesis are stimulated  Glucose level normalizes to baseline level (normoglycemia). This entire process takes an average of two hours for most adults. Downloaded by Caila Mae Dacquel ([email protected])  lOMoARcPSD|29614747 CLINICAL CHEMISTRY Carbohydrates ❖ Metabolism: GLYCOLYSIS (Cytosol): ❖ Metabolism: 3 MAJOR PATHWAYS OF GLYCOLYSIS PHASE 1: Energy is consumed EMBDEN-MEYERHOF-PARNAS (EMP) PATHWAY 1. Phosphorylation of glucose on C6 into glucose-6-phosphate and trapping  Most common pathway – anaerobic inside the cell  Steps: Glucose →converted to glucose-6-phosphate Pyruvate enters the mitochondrion and is converted into catalyzed by hexokinase acetyl-coenzyme A (acetyl-CoA) ATP →hydrolyzed to ADP Acetyl-coenzyme A then enters the citric acid cycle 2. Isomerization of glucose-6-phosphate to fructose 6-phosphate /tricarboxylic acid (TCA)/Krebs cycle where it is oxidized into CO2, H2O and ATP Glucose-6-phosphate →converted to fructose-6-phosphate catalyzed by phosphoglucomutase  Glycerol released from the hydrolysis of triglycerides can enter at 3- 3. Phosphorylation of fructose-6-phosphate on C1 phosphoglycerate Fructose-6-phosphate → converted to fructose-1,6-  Fatty acids and ketones and some amino acids are converted or biphosphate catalyzed by phosphofructokinase catabolized to acetyl-CoA (part of the TCA cycle)  Other amino acids enter the pathway as pyruvate or as deaminated ATP →hydrolyzed to ADP a-ketoacids and a-oxoacids  Gluconeogenesis 4. Split of fructose-1,6-bisphosphate into isomers o conversion of amino acids by the liver and other specialized Fructose-1,6-bphosphate →split into glyceraldehyde-3- tissue (e.g. kidney) to substrates that can be converted to phosphate (GAP) and dihydroxyacetone phosphate (DHAP), glucose catalyzed by aldolase o encompasses the conversion of glycerol, lactate, and pyruvate to glucose PHASE 2: Energy is produced  Anaerobic glycolysis 5. Conversion of DHAP into GAP. GAP is a substrate for the next step in o important for tissue (e.g. muscle) which often have important glycolysis so all of DHAP is eventually depleted → 2 molecules of GAP are energy requirements without an adequate oxygen supply formed from each molecule of glucose o these tissues can derive ATP from glucose in an oxygen- Dihydroxyacetone phosphate (DHAP) →converted to deficient environment by converting pyruvic acid into lactic Glyceraldehyde-3-phosphate (GAP), catalyzed by triose- acid phosphate isomerase o lactic acid diffuses from the muscle cell, enters the systemic circulation, and is then taken up and used by the liver 6. Dehydrogenation and C1 phosphorylation of GAP o for anaerobic glycolysis to occur: Glyceraldehyde-3-phosphate (GAP) →converted to 1,3- = 2 mol of ATP must be consumed for each mole of glucose bisphosphoglycerate, catalyzed by glyceraldehyde 3- = however, 4 mol of ATP are directly produced, resulting in a net phosphate dehydrogenase (GAPDH) gain of 2 mol of ATP NAD →reduced to NADH H+ HEXOSE MONOPHOSPHATE (HMP) SHUNT  Pentose Phosphate Shunt 7. Hydrolysis of the high energy bond at C1 by phosphoglycerate kinase yielding  responsible of the synthesis of reduced glutathione and NADPH to ATP and the product 3-phosphoglycerate protect cells from oxidative stress 1,3-bisphosphoglycerate →converted to 3-phosphoglycerate,  side pathway from the anaerobic glycolytic pathway catalyzed by phosphoglycerate kinase o a detour of glucose-6-phosphate from the glycolytic pathway to become 6-phosphogluconic acid = permits the formation of ADP →phosphorylated to ATP ribose-5-phosphate and NADP in its reduced form (NADPH) o NADPH 8. Shifting of phosphate from C3 to C2  important to erythrocytes that lack mitochondria and are 3-phosphoglycerate →converted to 2-phosphoglycerate, therefore incapable of the TCA cycle catalyzed by phosphoglycerate mutase  its reducing power is required for the protection of the cell from oxidative and free radical damage 9. Dehydration of 2-phosphoglycerate that utilizes Mg2+  without NADPH, the lipid bilayer membrane of the cell 2-phosphoglycerate → converted to phosphoenolpyruvate, and critical enzymes would eventually be destroyed = cell catalyzed by enolase death permits pentoses (e.g. ribose) to enter the glycolytic pathway 10. Hydrolysis of the high energy bond Phosphoenolpyruvate → converted to pyruvate, catalyzed by GLYCOGENESIS pyruvate kinase  glucose can be stored as glycogen when the cell’s energy ADP →phosphorylated to ATP requirements are being met 11. Net reaction: glucose-6-phosphate → glucose-1-phosphate → uridine diphosphoglucose → glycogen, catalyzed by glycogen synthase Glucose + 2 ADP + 2 phosphate → 2 pyruvate + 2 ATP + 2 NADH  several tissues are capable of the synthesis of glycogen 12. Pyruvate can: o liver synthesizes glucose-6-phosphatase (without this - enter EMP pathway enzyme, glucose is trapped in the glycolytic pathway) - enter HMP shunt o muscle cells do not synthesize glucose-6-phosphatase = - enter glycogenesis incapable of dephosphorylating glucose  In the presence of O2, pyruvate →oxidized to CO2  In the absence of O2, pyruvate →fermented to lactate or ethanol Downloaded by Caila Mae Dacquel ([email protected])  lOMoARcPSD|29614747 CLINICAL CHEMISTRY Carbohydrates ❖ Metabolism: ANCILLARY PATHWAYS OF GLYCOLYSIS HYPERGLYCEMIC METHEMOGLOBIN REDUCTASE PATHWAY Glucagon  maintains iron in the ferrous (Fe2+) state since ferric (Fe3+) are o primary hyperglycemic hormone responsible for increasing incapable of binding oxygen glucose levels o synthesized by the α-cells of islets of Langerhans in the pancreas and the L cells of the small distal bowel LUEBERING-RAPAPORT PATHWAY o released during stress and fasting states  responsible for the synthesis of 2,3-diphosphoglycerate to o Functions: enhance oxygen delivery to tissues  increase plasma glucose levels by glycogenolysis in the  hemoglobin has higher affinity to 2,3-DPG than oxygen liver  increase amino acids by gluconeogenesis ❖ Metabolism: REGULATION  DURING POST-PRANDIAL STATE Somatostatin o ↑Insulin to glucagon ratio = anabolism o produced by the δ-cells (delta) of the islets of Langerhans of the o Glycogenesis: Hyperglycemia stimulates insulin secretion pancreas (5-105%) promoting cellular uptake of glucose in insulin-sensitive o major inhibitory hormone tissues o net effect on glucose level - increase  DURING SHORT FASTING STATE o Function: increases plasma glucose levels by the inhibition of o ↓Insulin to glucagon ratio = catabolism pancreatic hormones (insulin, glucagon, PP) and pituitary o Glycogenolysis: The blood glucose level is kept constant hormones (growth hormone, thyrotropin) by mobilizing the glycogen stores in the liver Glucocorticoids  DURING LONG FAST STATE (>1 DAY) o Gluconeogenesis: body uses glucose from non- o primarily cortisol carbohydrate sources (amino acids, glycerol, pyruvate) o released from the adrenal cortex (zona fasciculata) on stimulation by adrenocorticotropic hormone (ACTH)  Pancreas: o Cushing’s syndrome/disease = elevated o Endocrine pancreas: Islets of Langerhans o Function: increases plasma glucose by decreasing intestinal  Beta cells - insulin, islet amyloid polypeptide (IAPP) entry into the cell and increasing gluconeogenesis, liver or amylin glycogen, and lipolysis  Alpha cells - glucagon  Delta cells - somatostatin Epinephrine  PP/F cells - pancreatic polypeptide o produced by the chromaffin cells of the adrenal medulla o Exocrine pancreas: Duct cells o released during times of stress  Duct cells - bicarbonate ions, secretion controlled o Pheochromocytoma = elevated by secretin o Functions:  Acinar cells - digestive enzymes pancreatic  increases plasma glucose by inhibiting insulin secretion amylase, lipase, trypsinogen and  increasing glycogenolysis chymotrypsinogen, secretion controlled by  promoting lipolysis cholecystokinin (formerly pancreozymin)  Major Hormones: Growth Hormone (Somatotropin) HYPOGLYCEMIC o release from the anterior pituitary is stimulated by decreased Insulin glucose levels and inhibited by increased glucose o primary hormone responsible for the entry of glucose into the o Function: increases plasma glucose by decreasing the entry of cell glucose into the cells and increasing glycolysis o synthesized by the β-cells of islets of Langerhans in the pancreas ACTH o processed from a larger precursor molecule called proinsulin o decreased levels of cortisol stimulate the anterior pituitary to in the beta cells - proinsulin is cleaved into insulin and C- release ACTH peptide o Function:  C-peptide and insulin are produced in equimolar  stimulates the adrenal cortex to release cortisol amounts into the portal vein  increases plasma glucose levels by converting liver  C-peptide:insulin serum ratio = 5:1 to 15:1 (due to glycogen to glucose and promoting gluconeogenesis increased hepatic clearance) o normally released when glucose levels are high and is not Thyroxine released when glucose levels are decreased o stimulated by the production of thyroid-stimulating hormone o only hormone that decreases glucose levels and can be o secreted by the follicular cells of the thyroid gland referred to as a hypoglycemic agent o Function: increases plasma glucose levels by increasing o Functions: glycogenolysis, gluconeogenesis, and intestinal absorption of  release of insulin causes an increased movement of glucose glucose into the cells and increased glucose metabolism Human placental lactogen  decreases plasma glucose levels by increasing the o insulin antagonist transport entry of glucose in muscle and adipose tissue by way of nonspecific receptors  regulates glucose by increasing glycogenesis, lipogenesis, and glycolysis and inhibiting glycogenolysis  enhances membrane permeability to cells in the liver, muscle, and adipose tissue  alters the glucose metabolic pathways Downloaded by Caila Mae Dacquel ([email protected])  lOMoARcPSD|29614747 CLINICAL CHEMISTRY Carbohydrates  Autoantibodies to zinc transporter 8 (ZnT8) o breakdown of glycogen to glucose for use as o Associated with HLA-DR3, HLA-DR4 (encoded by MHC energy Glycogenolysis Class II genes on chromosome 6) o glycogen is converted back to glucose-6- phosphate for entry into the glycolytic pathway o Upper limit of 110 mg/dL on the fasting plasma glucose is designated as the upper limit of normal blood glucose o conversion of glucose to glycogen for storage o Markers that can be found in 85% to 90% of individuals  dietary glucose and other carbohydrates with fasting hyperglycemia: either can be used by the liver and other  Islet cell autoantibodies cells for energy or can be stored as glycogen  Insulin autoantibodies Glycogenesis for later use  Glutamic acid decarboxylase autoantibodies  when the supply of glucose is low, the liver will use glycogen and other substrates (e.g.  Tyrosine phosphatase IA-2 and IA-2B autoantibodies glycerol, lactic acid, amino acids) to elevate o Characteristics: the blood glucose  abrupt onset – usually initiated by an environmental factor or infection (usually a virus) in individuals with Lipogenesis o conversion of carbohydrates to fatty acids a genetic predisposition  insulin dependence Lipolysis o decomposition of fat  ketosis tendency o Signs and symptoms:  polydipsia (excessive thirst) HYPERGLYCEMIA  polyphagia (increased food intake) ❖ Laboratory Findings:  polyuria (excessive urine production) INCREASED DECREASED  rapid weight loss  plasma glucose  blood and urine pH = acidosis  hyperventilation  urinary glucose  plasma sodium  mental confusion  urine specific gravity o hyponatremia  possible loss of consciousness  serum osmolality o due to polyuria and shift of o Complications:  plasma potassium water from cells  Microvascular: nephropathy, neuropathy and o hyperkalemia o serum sodium retinopathy o due to cellular shift secondary concentration decreases by  Macrovascular: atherosclerosis to acidosis 1.6 mmol/L for every 100  Diabetic ketoacidosis (DKA)  ketones in serum or urine mg/dL increase in glucose  A serious and potentially fatal hyperglycemic  anion gap  pCO2 = Kussmaul Kien or deep condition requiring urgent treatment rapid respiration  Associated with nausea, vomiting, abdominal  bicarbonate pain, electrolyte disturbances, and severe ❖ during a hyperglycemia state (in healthy patients) insulin is dehydration secreted by the β-cells of the pancreatic islets of Langerhans  Beta-hydroxybutyrate (ketone body) is high and ❖ caused by an imbalance of hormones falls with treatment whereas acetoacetic acid ❖ Clinical Manifestation: and acetone rise on treatment Diabetes Mellitus  Reagent strips for detection of ketones is not used to monitor recovery for diabetic  group of metabolic diseases characterized by hyperglycemia ketoacidosis since the strip is not sensitive to resulting from defects in insulin secretion, insulin action, or both presence of beta-hydroxybutyrate.  Associated Conditions:  Direct measurement of β-hydroxybutyrate is o End-stage renal disease - treated, leading cause favored over nitroprusside-based tests. o Non-traumatic amputations – most common cause  Anion gap is used to monitor recovery from DKA o Diabetic neuropathy - nerve damage occurs in 60% to 70% o Idiopathic type 1 diabetes of people with diabetes  form of type 1 diabetes o New blindness – foremost cause in adults ages 20-74 years  has no known etiology o Ketosis - develops in DM from excessive synthesis of acetyl-  strongly inherited CoA which can be reversed by insulin administration  does not have β-cell autoimmunity o Atherosclerotic disease – relates to most diabetes-related  episodic requirements for insulin replacement deaths (two to four times more likely to have heart disease and cerebrovascular disease) TYPE 2 DIABETES MELLITUS  Classifications: National Diabetes Data Group (1979) o Former names: non-insulin dependent DM, adult- TYPE 1 DIABETES MELLITUS type/maturity-onset DM, stable diabetes, ketosis- o Former names: Insulin-dependent diabetes mellitus, resistant, receptor-deficient DM juvenile onset diabetes mellitus, Brittle diabetes, Ketosis- o Most common type of diabetes - 90% of Americans prone diabetes o Most patients in this type are obese or have an increased o Represents approximately 10% of all cases of diabetes percentage of body fat distribution in the abdominal o Commonly occurs in childhood and adolescence region o Characterized by autoimmune (Type IV hypersensitivity) o Characterized by relative insulin resistance with insulin beta cell destruction and a tendency to ketoacidosis secretory defects  cellular-mediated autoimmune destruction of  C-peptide levels are measurable with a reduction in insulin-producing beta cells of the pancreas, beta cell mass over time causing an absolute deficiency in insulin production  insulin is not absent and may present as  absence of insulin with an excess of glucagon hyperinsulinemia with attenuated glucagon permits gluconeogenesis and lipolysis to occur o Characteristics:  autoantibodies responsible for beta cell destruction:  adult onset of the disease  Antibody to GAD65: highest sensitivity (91%),  milder symptoms more common in adults  ketoacidosis seldom occurring  Insulin autoantibodies (IAAs): more common in  fatty acid oxidation is inhibited - causes fatty acids children to be incorporated into triglycerides for release as  Autoantibodies to insulinoma-associated very low-density lipoproteins protein 2 (IA-2) o Signs and symptoms: Milder Downloaded by Caila Mae Dacquel ([email protected])  lOMoARcPSD|29614747 CLINICAL CHEMISTRY Carbohydrates o Laboratory Diagnosis: o Characteristics and prognosis of this form of diabetes  Hypertension, vascular disease or dyslipidemia depend on the primary disorder (HDL cholesterol ≤35 mg/dL and/or triglyceride level o Maturity-onset diabetes of youth - rare form of diabetes ≥250 mg/ dL) that is inherited in an autosomal dominant fashion  HbA1c of 5.7% or greater  Impaired fasting glucose or impaired glucose  Diagnosis Criteria: DIABETES MELLITUS tolerance HbA1c (glycated ≥ 6.5%  Other conditions associated with insulin resistance hemoglobin) o at least 2 occasions (i.e., acanthosis nigricans) ≥ 126 mg/dL or 7.0 mmol/  Elevated plasma glucose = >1,000 mg/dL (55 mmol/L) FBG o at least 2 occasions  Normal or elevated plasma sodium and potassium o obtained after 8-hour fast  Slightly decreased bicarbonate OGTT with a 2-hour ≥ 200 mg/dL or 11.1 mmol/L  Elevated blood urea nitrogen (BUN) and creatinine postload (75 g glucose o at least 2 occasions  Elevated osmolality = >320 mOsm/dl load) RBG + Symptoms ≥ 200 mg/dL NOTE: Gross elevation in glucose and osmolality, the elevation in BUN, and the NOTE: Any of the first three methods are considered appropriate for the absence of ketones distinguish this condition from diabetic ketoacidosis diagnosis of diabetes o Complications: o Point-of-care assay methods for either plasma glucose or  Nonketotic hyperosmolar coma – untreated, due to HbA1c are not recommended for diagnosis overproduction of glucose accompanied by severe o Group of individuals who did not meet the criteria of diabetes dehydration, electrolyte imbalance (low Na, high K) and mellitus but who have glucose levels above normal must be increased BUN and creatinine placed into three categories for the risk of developing  Respiratory distress syndrome, hypocalcemia, diabetes: hyperbilirubinemia - infants born to mothers with diabetes PREDIABETES o Risk Factors:  Impaired fasting glucose category = individuals with  Overweight (BMI ≥25 kg/m2) fasting glucose levels ≥100 mg/dL but