notes on CHO metab

8/7/2019 notes on CHO metab

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From the notes of Co-Neil Relato and Kathrina Virtusio Page 2 of 6 Brought to you by the Super Cool Non-Nerdy, Ortigas Study Club (SCNNOSC) of the UERMMMCI College of Medicine and friends.

DISORDERS OF CARBOHYDRATE (CHO) METABOLISM1.

Hyperglycemia raised plasma glucose

2.

Hypoglycemia decreased plasma glucose3.

Normal or lowered plasma glucose but still with problemsof glucose metabolism

DIABETES MELLITUS

Chronic metabolic disorder associated with increase bloodsugar level secondary to reduced insulin or impairedinsulin utilization

Part of metabolic syndrome (patients with hyperuricemia,hyperlipidemia, etc.)

Associated with cerebrovascular accidents, angiopathy,microvascular/cardiovascular (ischemic heart disease)disease, retinopathies, neuropathy (sensorimotor), andthe more dreaded renal complication (diabetic nepropathy

chronic renal insufficiency/renal failure); acceleratedatherosclerosis and hypertension

Etiologic Classification of Diabetes MellitusType 1 (juvenile type)

Beta cell destruction usually leading to absolute insulindeficiency

Immune-mediated, idiopathic

Diabetic ketoacidosis (DKA) common

Type 2

May range from predominantly insulin resistance (peripheral resistance particularly the muscle) with relativeinsulin deficiency to a predominantly secretory defect withinsulin resistance

DKA NOT common

Gestational DM (GDM)Other Specific Types

Genetic defects of beta cell function

Genetic defects in insulin action

Diseases of the exocrine pancreas

Endocrinopathies*

Drug or chemical-induced*

Infections

Uncommon forms of immune-mediated diabetes

*usual causes

DIAGNOSTIC CRITERIA1. History (history alone or on lab results alone do NOT suffice; itshould be symptoms plus lab result [* see next table ])

Symptoms : hunger, thirst, weight loss

Triad: polydipsia, polyuria, polyphagia

LABORATORY CRITERIA FOR DIAGNOSIS OF DM

** random plasma glucose (aka random blood sugar [RBS]); fasting plasmaglucose (fasting blood sugar [FBS]); post-load glucose (post-prandial glucose[PPG]); OGTT (oral glucose challenge test [OGCT])**OGTT: glucose is dissolved in 1 glass of water (to be consumed in5 minutes) determine glucose level after 2 hours (blood glucoseshould normally go down after 2 hours) if >200, possible

diabetes.**The above criteria should be confirmed by repeat testing on adifferent day. The 3-hour OGTT is NOT recommended for routineclinical use.

** impaired fasting glucose (IFG); impaired glucose tolerance (IGT)** Patients with IFG and IGT are NOT immediately labeled asdiabetic; this only signifies that they are at risk for developingdiabetes in the future.**OGTT/OGCT: 75 g glucose for non-pregnant and 100 g glucose forpregnant check glucose level after 30 minutes, 1 hour, 2 hours,and 3 hours

Laboratory Dx of DM

RBS, FBS

Post prandial blood sugar/ OGTT

Glycosylated Hb monitors efficacy of treatment

Ketone to detect DKA

Urine glucose home monitoring tool (self-test)

Other tests to monitor DM complication

Renal function test: creatinine, Creatinineclearance, BUNUrine albumin, microalbuminemia: to check forimpending diabetic nepropathyLipid profileRenal infection screen (urinalysis): DM patientsprone to renal infection

Random blood sugar

Blood sugar level taken at any time of the day

Values = 45- 130mg/dL or 2.5 to 7.2 mmol/L

Upper limit of 180 mg/dL or 10.0 mmol/L for > 65 year-old healthy patient is acceptable

Fasting Blood Sugar

Blood sugar level taken after overnight fast (at least 8 hrsor 12-14 hrs recommended; you can actually have FBS inthe afternoon as long as you have a minimum of 8 hoursfast)

Plasma specimen collected after 12 14 hour fast


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Overnight fasting glucose concentration between 50 and110 mg/dl ( 2.8 6.2 mmol/l ) accepted normal value

Diabetes mellitus can be dx by:

glucose level >140 mg/dl (7.8mmol/L ) orconsistently elevated glucose on 2 separateoccasions (e.g. after a month)

2-hour Postprandial Plasma glucose or Post-oral glucose test

Simplest loading test

Measurement of plasma glucose concentration 2 hrs after

the px consumes a load containing 100g of carbohydrate(either in a sachet or the px is given a meal [i.e. 1 full cupof rice, 2 eggs, banana, fish or meat, or 2-4 slices of bread])

Screening test in diagnosing GDM

Abnormal: Venous plasma level > 200mg/dl (11.1 mmol/L); 150 gm CHO for 3 daysNO alcohol, unrestricted activity for 3 daysNOT done after acute illness, surgery, emotionalstress, trauma, pregnancy, inactivity due tochronic illness, hospitalization10 12 hrs fastingAVOID oral diuretics, contraceptives phenytoinbecause they have hyperglycemic effect

Loading dose :

Must be consumed within 5 min

Adults = 75 gms

Children = 1.75 gms / kg BW

Pregnant = 100 gms

After drinking, instruct patient to sit down andrest or NOT walk around too much.

Draw blood

after an 8-hour fast; after extracting the FBS (1 st blood extraction), give the glucose load.Extract another blood specimen at 30 (2 nd bloodextraction), 60 (3 rd), and 120 minutes (4 th) postglucose challengeIntrusive to the patient due to 4 bloodextractions

OGTT CriteriaPlasma Glucose( mmol/L )

Plasma Glucose( mmol/L )

0 min 120 minNon-diabetic 7 >11.1

** I think the abscissa should be hours and NOT days.

** normal (blue line): This is a typical behavior of an OGTT of a non-pregnant patient (75 g). When you give the glucose challenge, itmaximally increases after 30 minutes to 170-180 and normalizes tofasting levels at the 2 nd hour and 3 rd hour.** IGT (pink line): slightly elevated glucose at the fasting level,higher than normal level at 30 minutes (about 200), and does NOTreturn to normal limits at the 2 nd and 3 rd hour (still at 160-180).** Diabetic (yellow): elevated glucose at fasting (140), 250 or >300after 30 minutes, and also does NOT normalize in the 2 nd /3 rd hour.

* Maam did not discuss the details of this table.

**In many laboratories, urine sample is collected at the same timeas the plasma samples (OGTT).

Advantage correlation between any glycosuria and thecorresponding plasma glucose levels

Disadvantage cost; another stress for the patient (4 urinesamples are also required together with 4 extractions of blood)

Impaired Glucose Tolerance

Higher than normal plasma glucose but lower than thediagnostic values for DM

Precursor for Type II DM (may have preclinical DM)

Only about 25% develop into type II and rest go back tonormal depending on the persons lifestyle

Patients are more susceptible to macrovascular diseases(i.e. atherosclerosis)

Similar risk factors as DM II

OGTT Clinical use

Reflex testing for px with borderline FBS (110-140 gm/dl):means that if the FBS is within this range, the next step inthe algorithm is OGTT.

Adjunct to diagnose IGT and IFG (as a confirmatory test)

Gold standard for dx of gestational DM

OGTT is NOT indicated in:

Persistent fasting hyperglycemia (> 140 mg/dl )

Persistent fasting normoglycemia(< 110 mg/dl )

Px with s/sx of DM with FBS > 200 mg/dl (this is already adiagnosis of DM so you do NOT need to confirm it withOGTT)

Secondary DM

Evaluation of reactive hypoglycemia

dx of DM in children (because the reference values arethat of the adults)

Ancillary TestsUrine Tests (Dipstick Method)

Principle: There is a renal threshold for glucose in the renaltubules (blood glucose 180 mg/dl). If this value isexceeded, glucose spills off into the urine.

Diagnostic reagent: glucose oxidase (enzymatic reagent)impregnated in a strip checks for enzyme reduction of the glucose

URINE "GLUCOSE"

lacks sensitivity = positivity in diseasepoor specificity = negativity in health

GLUCOSE LEVEL

0

100

200

300

0 0.5 1 2 3

DAYS

GLUCOSE

NORMAL

IMPAIRED

TOLERANCE

DIABETIC


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Problems

renal threshold variable 6 to 15 mg/dL thereforelacks sensitivity and has poor specificityinterferences : Clinitest / Glucose oxidase stripsif urine test is positive, a confirmatory blood testis NEEDED; do NOT presume that if the result inthe dipstick is 1+, then the blood sugar is 180.This is due to the variability in renal threshold

Glycosylated proteins

Glycosylated haemoglobin (HbA1c)

to monitor blood sugar levels for an extendedperiod of timeto monitor patient compliance to treatmentregimento monitor adequacy of blood glucose controlstable; most importanta form of fetal hemoglobinHbA1c LGI reference range 4.6-6.5%; 6%indicates good control and level >8% indicatesaction is neededglucose canNOT be dissociated from hemoglobinso HbA1c indicates cumulative glucose exposure

for the preceeding 2-3 months (3 months beingthe life expectancy of a normal RBC)Glucose binds continuously and IRreversibly withHb during life span of RBC (120 days)Disadvantage: affected by altered red cellsurvival (canNOT be used inhemoglobinopathies, thalassemia, haemolyticdse because of shortened RBC survival)If with good diabetic control, test HbA1c q6months; if poor control, test quarterly.

Fructosamine

mirrors glycosylation of all serum proteinsindicates previous 2-3 weeks glycaemic exposureused pregnancy/children in some sites

Glycosylated albuminindicates previous several days glycaemicexposurenot commonly used

Glycosylated HB (HbA1c)

Indicates average plasma glucose level for 6 to 12 weeks

Clinical use :

monitor diabetic px compliance

a lot of patients cheat blood glucose bydieting for a week before they aretested; a px canNOT cheat HbA1clevels

index of diabetic control (direct relationship of poor control and increased complication)predicts development and progression of microvascular complication

Dietary preparation not required

N: 4 8 % (*Maam said 4-6%)

Can estimate the mean daily glucose level

mean daily carbohydrate (CHO) level in mg/dl =10 x (HbA1c value + 4)

Interpretation :

Increased levels implies poor diabetic controlwhen FBS is < 110 mg/dl, HbA1c is normal in 96%of caseswhen FBS is 110-125 mg/dl, HbA1c is normal in80% of caseswhen FBS is > 126 mg/dl, HbA1c is normal in>60% of cases

HbA1c in known diabetics

< 7 % indicates good diabetic control

10 % indicates fair diabetic control

13 20 % indicates poor diabetic control

Increased HbA1c levels in:

Presence of HbF (fetal hemoglobin)

Chronic renal failure

Post splenectomy

Iron deficiency anemia

Hypertriglycerenemia

Alcohol, lead and opiate toxicity

Salicylate treatment

Decreased HbA1c levels in:

Shortened RBC life span particularly in hemolytic anemias

Following transfusion

Pregnancy

Ingestion of large amounts of Vit C/E

Hemoglobinopathies

Recommendations of the International Expert CommitteeFor the diagnosis of diabetes:

The HbA1c is an accurate, precise measure of chronicglycaemic levels and correlates well with the risk of diabetes complications

It has several advantages over laboratory measures of glucose

DM is diagnosed when HbA1c is 6.5 %. Diagnosis should be confirmed with a repeat HbA1c test. Confirmation isnot required in symptomatic subjects with plasma glucoselevels >200 mg/dl (>11.1 mmol/l)

If HbA1c testing is not possible, previously recommendeddiagnostic methods (e.g., FBG or 2hPPG, withconfirmation) are acceptable

HbA1c testing is indicated in children in whom diabetes issuspected but the classic symptoms and a casual plasmaglucose >200 mg/dl (>11.1 mmol/l) are not found

Clinical implications

HbA1c for diabetes diagnosis offers greater convenienceand accuracy than glucose measurements and correlateswell withlong-term complications

HbA1c may be too expensive for routine use in some partsof world

HbA1c may be influenced by haemoglobin traits andprecluded for people with conditions that affect red cellturnover (haemolytic anaemia, chronic malaria)

HbA1c not gold standard for diabetes diagnosis, as nosingle assay can define the relationship between glucoseand vascular complications

**Micral Test: to test for microalbuminuria; to detect for thepresence of early renal nephropathy


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POC (Point of Care) testing for glucose

Portable, can be used for home testing, physician s officesor bedside

Uses a refractometer (about the size of a Blackberry)

Uses capillary whole blood

Skin is pricked and blood is put in strip impregnated withglucose oxidase. The strip is then put into therefractometer for reading

Principle: glucose oxidase enzymatic method

approximately 10-15% lower glucose readings than

venous sample

Used for immediately monitoring blood glucose levels

should NEVER be used to diagnose DM or hypoglycemicdisorders; it is only used to monitor blood glucoseparticularly in patients with DKA and hypoglycemicdisorders

Home glucose monitoring

Require a drop of whole blood obtained by fingerstick tobe applied to a reagent test strip

After incubation of color development, test is read byreflectance photometer

Strips usually use a a glucose oxidase enzymatic methodembedded in the strip

GESTATIONAL DIABETES

**Screening test is 2-hour postprandial glucose test (1 st step). Whenthe result is abnormal, do reflex confirmatory testing (OGTT).

**I dont know what values are to be followed. Hindi nya rin na-mentionwhich one. Pick one nalang. Halos pareho lang naman hehehe

Other lab tests for CHO disorders: ketone testingKETONE TESTING

The ketone bodies

beta-hydroxybutyric acidacetoacetic acidacetone which are products of fatty degradation

(diagnostic substance of choice)

Used in dx of DKA in type I DM

DKA

a serious and potentially fatal hyperglycemiccondition conversion of excess glucose intoketone bodiesS/Sx: nausea, vomiting, abdominal pain,electrolyte disturbances, mental obtundation,ocular disturbances, seizures, and severedehydrationCan go into coma


Renal testing in DM


*Non-diabetic renal disease is suspected when there is absence of diabetic retinopathy in a person with renal disease, there are urinaryabnormalities such as haematuria or casts, or when there is renaldisease without microalbuminuria or proteinuria.

Tests for Diabetic renal disease:

Urinary albumin:creatinine ratio (ACR)

Serum creatinine

Estimated Glomerular Filtration Rate (eGFR) reducedGFR means there is significant nephron mass loss

Urinalysis , micral test

Note : These tests are performed on px suspected withrenal complication or if there is proteinuria ormicroalbuminuria

These tests are repeated annually in px with DM

Albumin : creatinine ratio

provides an estimate of daily urinary albumin excretion.

Microalbuminuria cannot be detected on a conventionalurinary protein dip stick.


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Microalbuminuria is urinary albumin excretion between 30and 300 mg/day; above 300mg/day representsproteinuria.

ACR is best measured in the laboratory using a firstmorning urine sample where possible when the patient iswell.

An abnormal initial test requires confirmation by testingon two further occasions. If at least one of these tests ispositive microalbuminuria has been confirmed.

Complications of DM:

CVS, renal, micro-angiopathy, retinopathy, neural

Other tests:

Lipid profile: at least annually if stable; if unstable, q3-4months until levels become stable and 6-12 monthsthereafter.

**It is important that management should be individualised

Parameter Optimal ValueTotal cholesterol < 4 mmol/LLDL cholesterol < 2.5 mmol/LHDL cholesterol > 1 mmol/LTC:HDL ratio < 4.5

Triglycerides < 1.7 mmol/LHbA1C < 7 mmol/L

Self-Monitoring blood glucose (SMBG)

People who take insulin should regularly self-monitorblood glucose

Makes use of a point of care device (i.e. a refractometer)

For people with non-insulin treated type 2 diabetes testingis most useful if patients use the results to learn and alterbehaviour, or medication.

...SMBG is most useful if patients use the results to learn,as part of an overall diabetes education package.

Other tests

Testing of LFTs (liver function test?) is recommended for px with DM

at diagnosis

at the start of antidiabetic drug therapy

at any other time indicated by clinical judgement

**In patients with type 1 diabetes, intermittent checks for otherautoimmune conditions may be useful. This could include testing forthyroid dysfunction or celiac disease.

**usually you give D 10W

HYPOGLYCEMIAClinical classification:

Critical illnesses (can have reactive hypoglycemia)

Hepatic/renal/cardiac failure

Sepsis

Malnutrition

Hormonal deficiencies of

Glucagon, epinephrine, cortisol, growthhormone

Endogenous hyperinsulinism

Pancreatic beta cell disorders

Tumor (insulinoma)

Non-tumor (nesidioblastosis or diffusehyperplasia of the pancreatic islet cells)

Autoimmune hypoglycemia

Insulin antibodies

Insulin receptor antibodies

Non-beta cell tumors (can present with non-resolvinghypoglycemia)

Mesenchymal: Fibrosarcoma, mesothelioma,rhabdomyosarcoma, leiomyosarcoma,liposarcoma, lymphosarcoma,hemangiopericytoma

Carcinomas: Hepatomas, adrenocortical tumors,hypernephroma, Wilms' tumor

Neurological and neuroendocrine tumors:Pheochromocytoma, carcinoid tumor,

neurofibroma

Hematologic: Leukemias, lymphoma, myeloma

INSULINOMA

Beta islet cell tumor

Caused by excess and inappropriate secretion of insulin byB cell tumors

Triad

Hypoglycemic attacks precipitated by fastingPlasma glucose

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notes on CHO metab