Diagnosis & Classification of Diabetes Mellitus

Diabetes
 Common and underdiagnosed
 Causes macro and microvascular events
 Reduces duration and quality of life
 Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from
defects in insulin secretion, insulin action, or both.
 The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and
failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.
 The long-term effects of diabetes mellitus include progressive development of the specific
complications of retinopathy with potential blindness, nephropathy that may lead to renal
failure, and/or neuropathy with risk of foot ulcers, amputation, Charcot joints, and features of
autonomic dysfunction, including sexual dysfunction. People with diabetes are at increased risk
of cardiovascular, peripheral vascular and cerebrovascular disease.
Definition
 A group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in
insulin secretion (lack of insulin production), resistance to insulin action, or a combination of
both.
o The chronic hyperglycemia is associated with long-term damage, dysfunction and failure
of multiple organ systems including the kidneys, eyes, nerves, heart, and blood vessels.
When should we do screening test?
 First, when the patient has symptoms typical of diabetes
 Second, when the patient has diabetes risk factors - fasting glucose concentration like a
screening test once a year
o We perform fasting glucose screening once every three years when we are a person
without risk factors but over 45 years of age.
 The diagnosis of diabetes in children during the first 6 months of life requires genetic testing for
neonatal diabetes
o In patients with cystic fibrosis, annual oral glucose tolerance test (OGTT) screening test
should be perfromed beyond 10 years of age to diagnose diabetes
Symptoms
 Polyuria
 Increased thirst
 Weight loss that cannot be explained by intended weight reduction
 Other, less typical symptoms and signs:
o Fatigue
o Somnolence
o Purulent skin lesions
o Inflammatory conditions of the genitourinary tract
Screening for Type 2 DM
 Testing for diabetes should be performed every three years, when we have patients without risk
factors but > 45 years of age.
 Risk groups should be tested annually regardless of age - screening test once a year.
 Overweight or obese subjects [body mass index (BMI) ≥ 25 kg/m2 and/or waist circumference >
80 cm (women) or > 94 cm (men)]
 Subjects with a family history of diabetes (in parents or siblings)
 Physically inactive subjects;
 Members of community or ethnic groups characterized by increased rates of diabetes;
  Those with prediabetes identified during previous testing;
 Women with a history of gestational diabetes; and women who gave birth to an infant with a
birth weight > 4 kg;
 Subjects with hypertension (≥ 140/90 mm Hg); cardiovascular disease and dyslipidemia [high-
density lipoprotein (HDL) cholesterol < 40 mg/dL (< 1.0 mmol/L) and/ /or triglycerides > 150
mg/dL (> 1.7 mmol/L)];
 Women with polycystic ovary syndrome;
Normoglycemia
 Fasting Glucose: 70-99 mg/dL (3.9-5.5 mmol/L)
 Postprandial glycemia: 71-140 mg/dL (3.9-7.8 mmol/L)
 Pregnant patients
o Fasting glucose: 70-90 mg/dL
o Postprandial glycemia: 71-140 mg/dL
Prediabetes: IFG and/or IGT
 Impaired fasting glucose (IFG): 100-125 mg/dL (5.6-6.9 mmol/L)
 Impaired glucose tolerance (IGT): 120- minute blood glucose at 120 minutes of OGTT 140-199
mg/dL (7.8-11 mmol/L)
Diabetes - one of the following criteria:
 Symptoms of hyperglycemia and random (occasional) blood glucose level ≥ 200 mg/dL (≥ 11.1
mmol/L)
 Fasting blood glucose ≥ 126 mg/dL (≥ 7.0 mmol/L) on two occasions;
 Blood glucose at 120 minutes of OGTT ≥ 200 mg/ dL (≥ 11.1 mmol/L);
 HbA1c level ≥ 6.5% (≥ 48 mmol/mol)
Conversion of mg/dL & mmol/L
 To convert to mg/dL from mmol/L,
o multiply mmol/L by 18.
o Example: 10 mmol/L x 18 = 180 mg/dL.X or less
 To convert to mmol / L from mg / dL
o divide by 18.
o Example 360 mg / dL: 18 = 20 mmol / L
Preferred Method of Diagnosing diabetes
 The preferred test for diagnosing diabetes is the measurement of the fating plasma glucose
level - and this is a screening test!!!
 Glucose can be measured from serum, plasma or whole blood ( < 15%)
 Serum or plasma must be separated from the cells within 1 hour to prevent substantial loss of
glucose by the cellular fraction
 If this is not possible, the blood must be taken:
o add glycolysis inhibitors: Sodium fluoride (2.5 mg / ml),
sodium iodoacetate (0.5 mg / ml
o usually used together with anticoagulants such as oxalate or EDTA
 Sodium fluoride ions are often used as preservative of whole blood, particularly if analysis is
delayed.
 Why a tube with glycolysis inhibitors ?. Because Without them, glucose will be consumed by the
blood components and then your blood glucose will be low. Why an anticoagulant? because the
disintegrating blood cells would release glucose and this situation would lead to an increase in
glycaemia.
HBA1c
 HbA1c level in a laboratory using a NSGP- certified method
  HBA1c ≥ 6.5% (48 mmol/mol)

 
Oral Glucose Tolerance Test (OGTT)
 Contraindications for the test:
o Previously diagnosed diabetes
o Diseases of the gastrointestinal tract that may impede the test (malabsorption
syndromes, conditions after stomach resection)
o Acute conditions and disease!! ( myocardial infarction, recent stroke, uncontrolled
hyperthyroidism, steroid therapy, postoperative period, etc.)
 Injunctions
o Fasting glucose: 100-125 mg/dL (5.6 - 7.0 mmol/L)
o Glucose in the urine with normal fasting glucose
o As a screening test for pregnant women between the 24 and 28 week of pregnancy
 Preparation of the patient
o DO NOT change before testing the diet for at least 72 hours, and in particular limit the
consumption of carbohydrates
o The patient should not take drugs with a diabetogenic effect - steroids, beta-blockers,
statins, thiazide diuretics
o The patient should report for the examination in the morning, on an empty stomach,
after at least 8-10 hours after taking the last meal, rested, after a good nights sleep
 Performing the test
o Taking the venous blood sample for the determination of plasma glucose
o Glucose load - the patient drinks 75 g of glucose (children 1.75 g/kg, max. 75 g) dissolved
in 250-300ml of water in 5 minutes; after loading, the patient remains at rest, in a sitting
position
o After 120 minutes after drinking glucose, a second sample of venous blood should be
taken to determine plasma glucose
Diabetes + Pregnancy
 Universal screening for hyperglycemia during pregnancy is recommended in Poland. Screening is
recommended at the first and third trimester (24-28 hbd)
 All pregnant women (without risk factors) should be evaluated for dysglycemia. Initial-screening
fasting blood glucose measurement to detect gestational hyperglycemia should be ordered early
during pregnancy, at the time of the first visit to a gynecologist.
 In pregnant women at risk a diagnostic test (OGTT with 75 g of glucose) should be ordered
already at the time of the first visit during pregnancy
 1. We always do a 3-point test for pregnant patients. We evaluate fasting glucose, 1 hour
and 2 hours after drinking 75 g of glucose.
2. Self-measured blood glucose values are recommended – fasting and before meals: 70–
90 mg/dL (3.9–5.0 mmol/L); maximum blood glucose level at one hour after a meal: <
140 mg/dL (< 7.8 mmol/L); before 2 and 4 AM > 70–90 mg/dL (> 3.9–5.0 mmol/L).
3. HbA1c level measurements are a tool to evaluate blood glucose control in women with
pre-pregnancy diabetes.
Risk Factors for Hyperglycemia in Pregnancy
 Pregnancy beyond 35 years of, multiparity (many births in the interview)
 Gestational diabetes during previous pregnancies, or history of macrosomia ( birth a child with a
large body weight (over 4 kg))
 Previous delivery of a neonate with a congenital anomaly or history of intrauterine fetal demise
 Arterial hypertension, overweight, obesity, family history of diabetes type 2
 PCOS— polycystic ovary syndrome
Diabetes + Pregnancy
1) I prenatal visit + risk factors (+)→ OGGT !!!
2) I prenatal visit + risk factors (-) : fasting glucose (FG
o FG < 92 mg/dl → OGGT 24-28 hbd !!!
o FG 92-125 mg/dl→ OGGT after I prenatal visit
o FG >126 mg/dl- we must check fasting glucose one more time, and if:
 FG>126 mg/dl- we can recognize diabetes (in) during pregnancy !!!
 FG 92-125 mg/dl- OGTT !!!
Diagnosis of GDM (Gestational Diabetes)
 OGTT (75g)
 In Fasting: 92-125
 1 hour: >180
 2 hours: > 153-200
 
Post-partum Recommendations
 Given that:
o GDM may be the first manifestation of type 2 diabetes and the incidence of diabetes
after delivery is in the range of 2.6% - 70% within 5 years
 It is recommended that OGTT be performed 6-12 weeks after delivery, followed by fasting blood
glucose determination once a year, before the next OGTT pregnancy is planned.
 Promotion of breastfeeding
Diagnosis of Diabetes in Pregnancy ("Normal" type of diabetes)
1. 1st prenatal visit fasting glucose > 126 mg/dL (TWICE) - diabetes in pregnancy
2. 1st prenatal visit with risk factors (+) - OGTT
i. In fasting: > 126mg/dL
ii. 1 hour: we do not take into account the result after 1 hour of the test in diagnosis of
diabetes in pregnancy
iii. 2 hours: > 200 mg/dL
Classifications of Diabetes
 Type 1 diabetes (autoimmune destruction of pancreatic beta cells, usually leading to absolute
insulin deficiency)
o Characteristic for children and adolescents
o Latent autoimmune diabetes in adults (LADA)
  Diabetes type 2 — progressive loss of the ability of pancreatic beta cells to secrete insulin
appropriately, with concomitant insulin resistance
 Hyperglycemia identified for the first time during pregnancy:
o Diabetes during pregnancy (Diabetes in pregnancy)
o Gestational diabetes.
 Other specific types of diabetes
o Genetically determined ( MODY- diabetes, mitochondrial diabetes, neneonatal diabetes)
o Diseases of the pancreas (pancreatitis, pancreatic injury and pancreatectomy, cancer,
cystic fibrosis, hemochromatosis, Fibrous- calcium pancreatopathy and others)
o Endocrinopathy (acromegaly, Cushing, pheochromocytoma, hyperthyroidism,
glucagonoma, somatostatinoma, aldosteronoma) !!!
o The influence of drugs or chemical substances (c. Nicotine, steroids, phenytoin,
thiazides, thyroid hormones, B-blockers)
Drug induced Hyperglycemia
 Atypical Antipsychotics: Alter receptor binding characteristics, leading to increased insulin
resistance.
 Beta-blockers: Inhibit insulin secretion.
 Calcium Channel Blockers: Inhibits secretion of insulin by interfering
with cytosolic calcium release.
 Immunosuppressants (used after organ transplants): ciclosporin, tacrolimus
 Corticosteroids: Cause peripheral insulin resistance and gluconeogenesis.
 Fluoroquinolones: Inhibits insulin secretion by blocking ATP sensitive potassium channels.
 Naicin: They cause increased insulin resistance due to increased free fatty acid mobilization.
 Phenothiazines: Inhibit insulin secretion.
 Protease Inhibitors: Inhibit the conversion of proinsulin to insulin.
 Thiazide Diuretics: Inhibit insulin secretion due to hypokalemia. They also cause increased
insulin resistance due to increased free fatty acid mobilization.
Diabetes & Pregnancy
1. Gestational diabetes mellitus: Hyperglycemia first detected at any time during pregnancy.
 Most women classified with gestational diabetes mellitus have normal glucose homeostasis
during the first half of the pregnancy and develop a relative insulin deficiency during the last
half of the pregnancy, leading to hyperglycemia.
o The hyperglycemia resolves in most women after delivery but places them at
increased risk of developing type 2 diabetes mellitus later in life.
2. Diabetes in pregnancy - Women with undiagnosed pre-pregnancy, asymptomatic type 2 or
type 1 diabetes, or other types of diabetes, detected for the first time during pregnancy.
o Diabetes in pregnancy - we recognize if the general conditions for the diagnosis of
diabetes are met, such as for the general population.
3. Pregestational diabetes mellitus (PGDM) — diabetes preexisting in a woman who becomes
pregnant (regardless of the diabetes type).
 
Clinical Problem
 We often have a problem with the differentiation of type 2 diabetes and type 1 LADA diabetes.
 The patient's phenotype, family history and accompanying diseases will help us in the
differential diagnosis
 We can do the c-peptide test (remember c-peptide is a great indicator of the endocrine capacity
of the pancreas- B cells (because c-peptide is formed in an equivalent concentration like insulin.
Both insulin and c-peptide are made from pre-proinsulin))
  But the most important test is the assessment of anti- GAD (glutamic acid decarboskylase)
antibodies.
Insulin Synthesis
 (11 Chromosome) Insulin gene
 5-10 min. Pre-proinsulin
 30 min Proinsulin
 60 min Insulin C-peptide
Differentiation of borderline forms - LADA type diabetes and type 2 diabetes mellitus
 Type 1 (LADA)
o No overweight
o Family history - autoimmune disease
o No hypertension
o C peptide low
o Non-specific complications of diabetes
o Current anti-GAD/ ICA antibodies
 Type 2
o Overweight and obesity
o Type 2 diabetes in the family
o The present hypertension or other features of the metabolic syndrome
o C peptide high
o Common micro- and/or macro- vascular complications when detecting diabetes
o No antibodies
Differentiation of boundary forms - Glucagon test (1 mg iv - C peptide in 6 min)
Peptide C (nmol/L) Recognition

< 0.35 Diabetes Type I (90% probability)

0.35 - 1.2 Intermediate values (p/body) - the need to assess anti-GAD

antibodies

>1.2 Diabetes Type II (90% probability)

 Type 1 diabetes mellitus (formerly called type I, IDDM or juvenile diabetes) is characterized by
beta cell destruction caused by an autoimmune process, usually leading to absolute insulin
deficiency.
 The onset is usually acute (with ketoacidosis), developing over a period of a few days to weeks.
 Over 95 percent of persons with type 1 diabetes mellitus develop the disease before the age of
25, with an equal incidence in both sexes and an increased prevalence in the white population.
 A family history of type 1 diabetes mellitus, gluten enteropathy (celiac disease) or other
endocrine autoimmune disease is often found.
 Most of these patients have the "immune-mediated form" of type 1 diabetes mellitus with islet
cell antibodies
 Markers of immune destruction: glutamic acid decarboxylase (GAD antibody),islet cell (ICA
antibody), insulin (IA-2, IA-2B antibody) anti-tyrosine phosphatase and anti- zinc antibodies
o Strong HLA association and often have other autoimmune disorders such as Hashimoto's
thyroiditis, Addison's Disease, Vitiligo or pernicious anemia
o A few patients (usually African/Asian origin) have no antibodies but have a similar
clinical presentation; consequently, they are included in this classification and their
disease is called the "idiopathic form" of type 1 diabetes mellitus
Autoantibodies - Frequency of Occurrence in Diabetes
 ICA: 70-80%
 IAA: 50% (mainly in children)
 Anti-GAD65: 70-80%
 Anti-IA-2: 60%
 More than 95% of patient at diagnosis of diabetes have at least one antibody
Antibodies
 Anti- islet cell autoantibodies and insulin autoantibodies are more characteristic of children and
classic type 1 diabetes.
 Anti GAD- glutamic acid decarboxylase autoantibodies- are more specific to type 1 LADA
diabetes.
Natural History of "Pre" - Type 1 Diabetes
 

 
Laboratory Features in DM1
 ↓ insulin ↓C-peptide
 Detectable autoantibodies:
o islet cell autoantibodies
o insulin autoantibodies
o glutamic acid decarboxylase autoantibodies
o Tyrosine phosphatase IA-2 and IA-2B autoantibodies
 Ketosis tendency (metabolic acidosis, ↑ketones in urinalysis and serum)
Diabetes Miletus Type II
 Type 2 diabetes mellitus (formerly called NIDDM, type II or adult-onset) is characterized by
insulin resistance in peripheral tissue and an insulin secretory defect of the beta cell.
 This is the most common form (90-95%) of diabetes mellitus and is highly associated with a
family history of diabetes, older age, obesity and lack of exercise.
 It is more common in women, especially women with a history of gestational diabetes, and in
Afro-Americans, Hispanics and Native Americans.
 The commonest form of the disease, accounting for 85-95% of all cases worldwide, affecting 5-
7% of the world’s population
 Insulin resistance impairs insulin’s metabolic actions on the liver (↑increasing hepatic glucose
production and raising basal blood glucose) and in skeletal muscle inhibiting normal glucose
uptake and utilization after meals)
  Insulin resistance probably precedes and may exacerbate β-cell failure by driving insulin
secretion in an attempt to maintain euglycemia.
Syndrome of Insulin Resistance
 Reaven's Syndrome, Syndrome X Metabolic Syndrome

 
What about before diabetes?
1. Insulin resistance
2. Compensatory hyperinsulinemia
3. Pre-diabetes - IGT + IFG
 We are currently trying to recognize pre-diabetic conditions as early as possible. Thanks to this,
we can treat patients much earlier before diabetes develops and complications of diabetes
appear.
 We have several tests for the diagnosis of insulin resistance - the most used is the HOMA index.
Insulin Resistance
 HOMA-IR stands for Homeostatic Model Assessment of Insulin Resistance
 Healthy Range: 1.0 (0.5 - 1.4)
 Less than 1.0 - Means you are Insulin-sensitive which is optimal
 Above 1.9 - Is indicative of Early Insulin Resistance
 Above 2.5 - Is indicative of Significant Insulin Resistance
 Remember that both values refer to the fasting state - where nothing has been eaten or drank
(other than water) for at least 8 hours before the blood sample is drawn.
 HOMA-IR = (insulin x glucose) / 22.5 for the glucose concentration in mmol/L,
 HOMA-IR = (insulin x glucose ) / 405 for glycemia in mg/dL.
o In both cases the insulin is in mU/L.
Insulin Resistance
 Matsuda index = 100,000 / ÷ fasting insulinemia (mU / ml) × fasting glucose (mg / dl) × average
concentration glucose value in the oral glucose test (OGTT) × average concentration insulinemia
in OGTT.
 Insulin resistance may be indicated by the index <7.3
Postprandial Hyperinsulinemia
 We recognize postprandial hyperinsulinemia when:
o Insulin after 1 hour of Oral Glucose loading test is above 70 uL/L
o Insulin after 2 hours of the ongoing glucose load test is above 30 ul/L
Diabetes Mellitus Type 2
 β-cell failure is less severe than in type 1 diabetes
 C-peptide positive patients and not susceptible to ketosis, because endogenous insulin
production is sufficient to prevent lipolysis and ketogenesis
 β-cell functions declines progressively over several years, leading first to IGT and then to overt
diabetes
 Because diabetes has usually been present for several years, micro- and macrovascular diabetic
complications are commonly found at diagnosis
 Type 2 diabetes is not a „mild” disease
 Chronic diabetic complications are common and potentially severe
 Coronary heart disease is 3-5 times commoner than in non-diabetic people, and up to 75% of
patients die from cardiovascular causes.
 Life expectancy for middle-aged patients is shortened by 5-10 years!!!
Laboratory Findings in DM
 Urinalysis:
o glycosuria
o ketonuria (also appears in starvation, high-fat diets, alcoholic ketoacidosis, fever)
o proteinuria – often the first sign of renal complications of diabetes
o albuminuria 30-300 mg/24 h
Glucosuria
 Under normal conditions, the glycemic threshold is 150-180 mg/dl.
 In pregnant women, this value is less than 150 mg / dl, which is why pregnant women may have
so-called physiological glucosuria.
 In diabetic kidney disease, the glycemic threshold increases to 300 mg / dl. This means that
despite significant hyperglycemia, eg 200 mg / dl, no glycosuria is found.
 Glucosuria can occur despite normal glycemia. This symptom is the result of dysfunction of
proximal renal tubules and is defined as renal glucose.
 Glucosuria will be present in diabetes patients treated with SGLT2 inhibitors
Ketones
 The ketone bodies are produced by the liver through metabolism of fatty acids to provide a
ready energy source from stored lipids at times of low carbohydrates availability
Ketogenesis
 A low level of ketone bodies is present in the body
 Production is increased:
o Diabetes mellitus
o Starvation
o High-fat diets
o Prolonged vomiting
o Glycogen storage disease
 The term ketonemia refers to the accumulation of ketones in blood
 Ketonuria – accumulation of ketones in urine
 The measurement of ketones is recommended for patients with type 1 diabetes during acute
illness, stress, pregnancy, elevated blood glucose levels above 300 mg/dl or when the patients
have signs of ketoacidosis
 The specimen requirement is fresh serum or urine
 The sample should be analyzed immediately
Proteinuria
 Physiological proteinuria - daily loss of protein <250 mg (occurs, among others, in conditions of
high physical effort)
 Pathological proteinuria - daily loss of protein in the urine is> 500 mg (some textbooks give>
300 mg)
 Proteinuria causes:
o Diabetes
o High blood pressure (hypertension)
o Kidney disease, pregnancy, urinary infection.
o Multiple myeloma, amyloidosis
o Drugs: ACE inhibitors (angiotensin-converting enzyme inhibitors) and ARB-s (angiotensin
receptor blockers)
 Albuminuria refers to the appearance of small but abnormal amounts of albumin in the urine. If
measured, this protein excretion is between 30 and 300 mg during a 24 hour period.
 Normal < 30 mg/24 h.
 A patient is determined to have microalbuminuria when 2 of 3 specimens collected within a 3-
6month period are abnormal - and this is the first symptom of diabetic kidney disease
Periodic Causes of Albuminuria
 Excessive physical effort
 Pregnancy
 Heart failure
 Hypertension
 Urinary tract infection
 Fever
 Excessive effort or standing for too long
Blood Glucose Self-Monitoring
 Blood glucose self-monitoring is an integral part of diabetes treatment.
 Patients should perform a daily blood glucose profile that includes readings at morning fast,
before (when they are treated by insulin therapy) and 60–120 minutes after each main meal,
and before bedtime and at night but not every day. Self control we should do before planned
physical activity, whenever hypoglycemia is suspected, and before activities associated with
particular dangers of hypoglycemia
  We use of blood glucose monitoring systems including : continuous glucose monitoring (CGM)
and flash glucose monitoring (FGM) and glucose meters
Glucose Meters
1. Gluco meters measure glucose in capillary blood, not plasma – you must always prick your
fingers.
2. A small drop of blood, obtained by pricking the skin with a lancet, is placed on a disposable test
strip that the meter reads and uses to calculate the blood glucose level. The meter then displays
the level in units of mg/dl or mmol/l.
3. It is recommended to use glucose meters that display plasma glucose level with the declared
margin of error of up to 15% for glucose levels ≥ 100 mg/dL (5.6 mmol/L) and 15 mg/dL (0.8
mmol/l) for glucose levels < 100 mg/dL (5.6 mmol/L)
Flash Glucose Monitors
1. Flash glucose monitors are a way of measuring your sugar levels without having to prick your
fingers. FGM assesses glycemia in interstitial fluid. Therefore, the condition of using FGM is
adequate hydration.
2. A flash glucose monitor is a small sensor that you wear just under your skin. It records your
glucose (sugar) levels continuously throughout the day and night. You can find out your levels by
scanning the sensor whenever you want to.
The sensor doesn’t actually measure your blood sugar level, it measures the amount of glucose
in the fluid that surrounds your body cells – called interstitial fluid. There is a small time delay
when checking this fluid, especially after eating or if you're exercising. So your flash glucose
monitor result isn't always exactly the same as your finger-prick result.
3. The sensor should be changed every 10-14 days
Continuous Glucose Monitoring
 A CGM (Continuous Glucose Monitoring) works through a tiny sensor inserted under your skin,
usually on your belly or arm. The sensor measures your interstitial glucose level, which is the
glucose found in the fluid between the cells. The sensor tests glucose every few minutes. A
transmitter wirelessly sends the information to a monitor (the monitor may be part of an insulin
pump or a separate device).
o CGMs are always on and recording glucose levels—whether you’re showering, working,
exercising, or sleeping
 We will need to replace the CGM sensor every 3 to 7 days, depending on the model.
HBA1c
 Hemoglobin A1c level reflects average blood glucose levels during the period of approximately 3
last months, with about 50% of HbA1c currently present in blood being formed during the last
month before the measurement
 Hemoglobin A1c level measurements should be performed using analytic methods certified by
the National Glycohemoglobin Standardization Program (NGSP) (http://www.ngsp.org). Point-
of-care testing for HbA1c is also possible when using methods and analyzers certified by NGSP.
 It has been suggested that diagnostic laboratories report HbA1c levels in SI units (mmol/mol) in
addition to traditional units.
1. The material for determining glycohemoglobin is whole venous blood collected for EDTA or
heparin or capillary blood collected in special heparinized capillaries and tubes, usually
containing a hemolytic reagent.
 The patient does not require any preparation before collecting the material, he does not need to
be on an empty stomach,
o although in lipemic samples the results of determinations by some methods may be
overstated.
 2. The determination should be carried out as soon as possible after sampling because glycation
also occurs in vitro to a degree depending on current glucose concentration.
 The durability of samples is influenced by the determination method, but it is generally allowed
to store the material for up to a week at + 4 ° C.
 With prolonged storage of whole blood or hemolysate, combinations of hemoglobin and
glutathione are formed, which interfere with the determinations made using chromatographic
methods
 Expressed as a percentage of total blood hemoglobin concentration gives a retrospective
assessment of the mean plasma glucose concentration during the preceding 8-12 weeks (3
months)
 The higher the percentage the poorer mean diabetic control
 Falsely low values may be found in patients with hemolytic disease renal failure and other,
hemoglobinopathies, variants of hemoglobin arising under the influence of drugs, alcohol or
uremia, hypertriglyceridemia, hyperbilirubinemia
 
Glycated Plasma Proteins - Fructosamine
1. T1 / 2 albumin is 14-20 days, therefore the concentration of its glycated form reflects the
average concentration of glucose in the blood during 2 weeks before the determination.
Glycated plasma proteins - fructosamine - is a ketoamine form formed after rearrangement of a
molecule formed after the glucose reaction with the e-amino group of lysine residues of
proteins, mainly albumin.
2. False levels of fructosamine may be associated with a decrease in protein levels or result from
changes in protein production in the body - malabsorption syndromes, bowel resection
conditions, intestinal inflammation, liver failure, nephrotic / nephritic syndrome + other kidney
diseases involving proteinuria, malnutrition / high protein diet , etc. High levels of ascorbic acid,
hemolysis, hyperthyroidism, and lipemia also affect fructosamine levels.
Target Values of Glycated Hemoglobin
 General criteria and type 2 diabetes, age> 65, if life-expectancy <10 years
o HbA1c 7% (53 mmol / mol)
 Other criteria
a) HbA1c - 6.5% (48 mmol / mol):
- type 1 diabetes, when there is a low risk of hypoglycaemia, short- term diabetes
mellitus, children and adolescents regardless of the type of the disease
- fasting and pre-meal glucose, also in self-control: 80-110 mg / dl (4.4-6.1 mmol / l),
postprandial glycemia (2h after the start of the meal) in self-control <140 mg / dL (7.8
mmol / l)];
b) HbA1c 8.0% (64 mmol / mol): patients with advanced age and / or diabetes mellitus with
macroangiopathic complications (previous myocardial infarction and / or stroke) and / or a
number of comorbidities;
Diabetes & Pregnancy (pre-pregnancy diabetes)
 HbA1c level < 6.5% (48 mmol/mol) in women with pre-pregnancy diabetes contemplating
pregnancy
 The value below <6.5% before pregnancy and in the first trimester of pregnancy.
 In the second and third trimester, glycosylated hemoglobin <6.0% is recommended if it is not
associated with an increased incidence of hypoglycemia.
Criteria of Adequate Lipid Profile Control:
 Non-HDL cholesterol level < 100 mg/dL (2.6 mmol/L) in diabetic subjects at very high
cardiovascular risk
  Non-HDL cholesterol level < 130 mg/dL (3.4. mmol/L) in diabetic subject at high cardiovascular
risk
 Non-HDL cholesterol level <145 mg/dL (3.7 mmol/L) in subjects <40 years of age with diabetes
type I but without vascular complications or other cardiovascular risk factors; - TG level < 150
mg/dL (< 1.7 mmol/L) - HDL cholesterol > 40 mg/dL (>1.0 mmol/L) [in women, higher by 10
mg/dL (0.275 mmol/L)]
o HDL M(man) >40 mg/dL (woman + 10 mg/dl)
o TG < 150 mg/dL
 
Criteria of Adequate Lipid Profile Control
 LDL-C level < 70 mg/dL (1.9 mmol/L) or reduction by at least 50% if baseline LDL-C level is 70–
135 mg/dL (1.9–3.5 mmol/L) in diabetic subjects at very high cardiovascular risk;
 LDL-C level < 100 mg/dL (2.6 mmol/L) or reduction by at least 50% if baseline LDL-C level is 100–
200 mg/dL (2.6–5.2 mmol/L) in diabetic subjects at high cardiovascular risk;
 LDL-C level < 115 mg/dl (3.0 mmol/L) in subjects at low or moderate cardiovascular risk (subjects
< 40 years of age with diabetes type 1 but without chronic complications and other
cardiovascular risk factors);
 
Criteria of Adequate Blood Pressure Control:
 Systolic Blood pressure < 130 mmHg
 Diastolic Blood pressure < 80 mmHg
 
Diabetes Acute Complications
 Diabetic hypoglycemia (complication of treatment)
 Diabetic ketoacidosis (mortality 5%)
 Nonketotic hyperosmolar state (mortality 15%)
 Lactate acidosis (mortality 50 %)
Hypoglycemia
 Glucose concentration ↓ 70 mg/dl
 Hypoglycemia classification by the International Hypoglycemia Study Group, 2017
 Alert glucose level (level 1) ≤ 70 mg/dL (≤ 3.9 mmol/L) Blood glucose level requiring treatment
with simple carbohydrates Indication for an adjustment of blood glucose lowering agent doses
 Clinically important hypoglycemia (level 2) < 54 mg/dL (< 3.0 mmol/L) Sufficiently low blood
glucose level to indicate clinically important hypoglycemia
 Severe hypoglycemia (level 3) No specific value
Hypoglycemia associated with severe cognitive impairment requiring external assistance for
recovery
 

 
Autonomic Reaction to Hypoglycemia

Diabetic Ketoacidosis
 Acute disorders of the Diabetic ketoacidosis metabolism of glucose, fats and proteins, water and
electrolytes and water and electrolyte balance caused by insulin deficiency.
 CAUSES:
o interruption or errors of insulin therapy,
o acute viral and bacterial infections,
o acute non-communicable diseases: heart attack, stroke,
o delay in the diagnosis of diabetes,
o the cause is difficult to determine (30%).
o Alcohol abuse, smoking
  Glucose↑250mg/dl(13.9mmol/l)
pH <7.35
Concentration of bicarbonate <18mmol / l Ketone bodies - present in urine or serum Anion gap>
10
 Anion gap = (Na+)- [ (Cl-)+(HCO3-) ]
 
Nonketotic Hyperosmolar State
 characteristic for Type 2 patients
Mechanism
 hyperglycemia --> hyperosmolarity --> polyuria --> dehydration
 the presence of some insulin inhibits lipolysis – no ketoacidosis
Symptoms
 hyperglycemia, hyperosmolarity
 dehydration – hypotension
 renal insufficiency, mental and neurologic signs,
 thrombosis
 coma, death
 
Hyperglycemic Hyperosmolar State
Causes:
 Most commonly develops due to a delayed diagnosis or inadequate treatment of diabetes type
2,
 in the course of stroke or myocardial infarction,
 following consumption of large amounts of alcohol,
 use of some diuretics,
 In patients with chronic kidney disease,
 Mental health problems, infection
 
Laboratory Diagnostic criteria of a Hyperglycemic Hyperosmolar state:
 Blood glucose > 600 mg/dL (> 33.3 mmol/L);
 pH > 7.30;
 Serum bicarbonate level > 15.0 mmol/L;
 Hypernatremia: corrected serum sodium level
(calculated using the formula given above) ≥ 150 mmol/L;
 Serum ketone bodies: absent/trace;
 Effective plasma osmolality > 320 mOsm/kg H2O.
 Effective plasma osmolality (mOsm/kg H2O) = 2 [Na+ (mmol/L)] + blood glucose (mmol/L) {2
[measured Na (mEq/L)] + [blood glucose (mg/dL)]/18}
 Normal plasma osmolality is 280–300 mOsm/kg H2O.
 
Lactic Acidosis
 Causes:
o Type A is due to cardiogenic shock, massive bleeding, septic shock, acute or chronic
respiratory failure (it is not characteristic for diabetes) but three fourths of diabetic
patients die due to cardiovascular causes; this condition may also occur in diabetic
patients;
 o Type B is due to causes other than hypoxemia. It develops in patients with diabetes,
liver disease, malignancies, and following ingestion of ethanol, biguanides, salicylates,
and methanol
 
Laboratory Diagnostic Criteria:
 Moderately elevated blood glucose (but may also be normal);
 Reduced blood pH (< 7.30), bicarbonate level 16 mmol/L (usually below ↓ 10mmol / l
 Lactate level > 5 mmol/L;
 Normal serum sodium level (may be reduced in alcohol abuse);
 Usually increased serum potassium level
 
Differential Diagnosis of Non-ketonic, Ketonic and lactate coma