ONMedU, Department of Internal medicine 1 with cardio

ONMedU, Department of Internal medicine 1 with cardio-vascular pathology course, Lecture №01.

Diabetes mellitus. Modern classification, etiology, pathogenesis, symptoms, diagnosis. Chronic

complications of Diabetes

Methodological recommendations on lecture, EPP “Medicine”, 4 course, International faculty,

Discipline “Endocrinology” Page 1

ODESA NATIONAL MEDICAL UNIVERSITY

Department of Internal medicine №1 with the cardiovascular pathology course

APPROVED by

Head of department

_________(prof. Karpenko I.I)

“27” September 2021

METHODOLOGICAL RECOMMENDATION ON THE LECTURE

Course: IV Faculty: International

Academic discipline “Endocrinology”

Lecture №01 Topic “Diabetes mellitus. Modern classification, etiology,

pathogenesis, symptoms, diagnosis. Chronic complications of Diabetes”

Odesa – 2021 y.

The lecture was created by

Assistant

___________ (Blikhar O.V.)

The lecture was discussed at

the methodical meeting of the

department

«27» September 2021 y.

Protocol № 2.






Lecture № 01

Topic: “Diabetes mellitus. Modern classification, etiology, pathogenesis,

symptoms, diagnosis. Chronic complications of Diabetes”

The goals of the lecture : explain the essence of the Diabetes mellitus, causes, role

in the etiopathogenesis of various factors, approaches to diagnosis and prevention.

Specific objectives of the lecture:

- give a modern definition of Diabetes mellitus;

- present generalized and systematized material on etiopathogenesis based on the

results of modern controlled clinical trials;

- present the basic concepts of classification, clinical features and diagnostic

approaches;

- to determine the basic principles of differential diagnosis with further substantiation

of final diagnosis based on the analysis of patient complaints, anamnesis, physical

symptoms, laboratory and instrumental examination data;

- explain the principles of treatment of Diabetes mellitus provided by national clinical

guidelines;

- to present modern methods of determining the prognosis and expert assessment of

the patient's ability to work based on the recommendations of the Ministry of Health

of Ukraine;

- to demonstrate the principles of medical ethics and deontology, to promote the

formation of a professionally significant structure of the doctor's personality on the

example of the peculiarities of working with patients.

Key words: Diabetes mellitus, hyperglycemia, autoimmune disease, obesity, HbA1c,

oral glucose tolerance test

Lecture plan and organizational structure

№ The main stages of the lecture

and their content

Goals in

levels of

abstraction

Type of lecture,

methods and means

of activating

students, equipment

Time

distribution

І

1.

2.

Preparatory stage

Setting a learning goal

Providing positive motivation

І

І

In accordance with

the publication

"Guidelines for

planning,

preparation and

analysis of lectures"

5%

(5 min)






ІІ

3.

The main stage

Teaching lecture material

according to the plan:

1. Relevance of the topic

2. Definition

3. Classification

4. Etiology and main links of

pathogenesis

5. Symptoms and signs

6. Diagnostic criteria

7. Main syndromes and

differential diagnosis

8. Criteria for the severity of

disease

9. Treatment

10. Prevention

ІІ

ІІ

ІІ

ІІ

ІІ

ІІ

ІІ

ІІ

ІІ

ІІ

Slide presentation of

lecture material

Extracts from

medical histories of

patients. Excerpts

from clinical

protocols of the

Ministry of Health

of Ukraine for the

provision of medical

care to patients.

85%

(75 min)

ІІІ

4.

5.

6.

The final stage

Lecture summary, general

conclusions

Answers to possible questions

Tasks for self-training

ІІІ

ІІІ

ІІІ

References,

questions, tasks

10%

(10 min)

Content of the lecture

Diabetes is a chronic disease that occurs either when the pancreas does not

produce enough insulin or when the body cannot effectively use the insulin it

produces. Insulin is a hormone that regulates blood sugar. Hyperglycaemia, or raised

blood sugar, is a common effect of uncontrolled diabetes and over time leads to

serious damage to many of the body's systems, especially the nerves and blood

vessels.

In 2014, 8.5% of adults aged 18 years and older had diabetes. In 2019, diabetes was

the direct cause of 1.5 million deaths. To present a more accurate picture of the

deaths causes by diabetes, however, deaths due to higher-than-optimal blood glucose

through cardiovascular disease, chronic kidney disease and tuberculosis should be

added. In 2012 (year of the latest available data), there were another 2.2 million

deaths due to high blood glucose.

Between 2000 and 2016, there was a 5% increase in premature mortality from

diabetes. In high-income countries the premature mortality rate due to diabetes

decreased from 2000 to 2010 but then increased in 2010-2016. In lower-middle-

income countries, the premature mortality rate due to diabetes increased across both

periods.






By contrast, the probability of dying from any one of the four main

noncommunicable diseases (cardiovascular diseases, cancer, chronic respiratory

diseases or diabetes) between the ages of 30 and 70 decreased by 18% globally

between 2000 and 2016.

Diabetes is a complex, chronic illness requiring continuous medical care with

multifactorial risk-reduction strategies beyond glycemic control. Ongoing diabetes

self-management education and support are critical to preventing acute complications

and reducing the risk of long-term complications. Significant evidence exists that

supports a range of interventions to improve diabetes outcomes.

Classification

Diabetes can be classified into the following general categories:

1. Type 1 diabetes (due to autoimmune β-cell destruction, usually leading to absolute

insulin deficiency, including latent autoimmune diabetes of adulthood)

2. Type 2 diabetes (due to a progressive loss of adequate β-cell insulin secretion

frequently on the background of insulin resistance)

3. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes

(such as neonatal diabetes and maturity-onset diabetes of the young), diseases of the

exocrine pancreas (such as cystic fibrosis and pancreatitis), and drug- or chemical-

induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AIDS, or

after organ transplantation)

4. Gestational diabetes mellitus (diabetes diagnosed in the second or third trimester of

pregnancy that was not clearly overt diabetes prior to gestation)

Type 1 Diabetes

This form, previously called “insulin-dependent diabetes” or “juvenile-onset

diabetes,” accounts for 5–10% of diabetes and is due to cellular-mediated

autoimmune destruction of the pancreatic β-cells. Autoimmune markers include islet

cell autoantibodies and autoantibodies to GAD (GAD65), insulin, the tyrosine

phosphatases IA-2 and IA-2β, and zinc transporter 8 (ZnT8).

Staging of type 1 diabetes

Stage 1 Stage 2 Stage 3

Characteristics

• Autoimmunity • Autoimmunity • New-onset

hyperglycemia

• Normoglycemia • Dysglycemia • Symptomatic

• Presymptomatic • Presymptomatic

Diagnostic • Multiple • Multiple • Clinical






Stage 1 Stage 2 Stage 3

criteria autoantibodies autoantibodies symptoms

• No IGT or IFG • Dysglycemia:

IFG and/or IGT

• Diabetes by

standard criteria

• FPG 100–125

mg/dL (5.6–6.9

mmol/L)

• 2-h PG 140–199

mg/dL (7.8–11.0

mmol/L)

• A1C 5.7–6.4%

(39–47 mmol/mol)

or ≥10% increase

in A1C

*FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose

tolerance; 2-h PG, 2-h plasma glucose.

Screening for Type 1 Diabetes Risk

Multiple studies indicate that measuring islet autoantibodies in individuals

genetically at risk for type 1 diabetes (e.g., relatives of those with type 1 diabetes or

individuals from the general population with type 1 diabetes–associated genetic

factors) identifies individuals who may develop type 1 diabetes. Such testing, coupled

with education about diabetes symptoms and close follow-up, may enable earlier

identification of type 1 diabetes onset.

Prediabetes and Type 2 Diabetes

Type 2 Diabetes

Type 2 diabetes, previously referred to as “noninsulin-dependent diabetes” or

“adult-onset diabetes,” accounts for 90–95% of all diabetes. This form encompasses

individuals who have relative (rather than absolute) insulin deficiency and have

peripheral insulin resistance. At least initially, and often throughout their lifetime,

these individuals may not need insulin treatment to survive.

There are various causes of type 2 diabetes. Although the specific etiologies

are not known, autoimmune destruction of β-cells does not occur, and patients do not

have any of the other known causes of diabetes. Most, but not all, patients with type 2

diabetes have overweight or obesity. Excess weight itself causes some degree of

insulin resistance.











Recommendations

Screening for prediabetes and type 2 diabetes with an informal assessment of risk

factors or validated tools should be considered in asymptomatic adults. B

Testing for prediabetes and/or type 2 diabetes in asymptomatic people should be

considered in adults of any age with overweight or obesity (BMI ≥25 kg/m2 or ≥23

kg/m2 in Asian Americans) and who have one or more additional risk factors for

diabetes. B

Testing for prediabetes and/or type 2 diabetes should be considered in women with

overweight or obesity planning pregnancy and/or who have one or more additional

risk factor for diabetes. C






For all people, testing should begin at age 45 years. B

If tests are normal, repeat testing carried out at a minimum of 3-year intervals is

reasonable, sooner with symptoms. C

To test for prediabetes and type 2 diabetes, fasting plasma glucose, 2-h plasma

glucose during 75-g oral glucose tolerance test, and A1C are equally appropriate B

In patients with prediabetes and type 2 diabetes, identify and treat other

cardiovascular disease risk factors. A

Risk-based screening for prediabetes and/or type 2 diabetes should be considered

after the onset of puberty or after 10 years of age, whichever occurs earlier, in

children and adolescents with overweight (BMI ≥85th percentile) or obesity (BMI

≥95th percentile) and who have one or more risk factor for diabetes. B

Patients with HIV should be screened for diabetes and prediabetes with a fasting

glucose test before starting antiretroviral therapy, at the time of switching

antiretroviral therapy, and 3−6 months after starting or switching antiretroviral

therapy. If initial screening results are normal, fasting glucose should be checked

annually. E

Criteria for testing for diabetes or prediabetes in asymptomatic adults

1. Testing should be considered in adults with overweight or obesity (BMI ≥25

kg/m2 or ≥23 kg/m2 in Asian Americans) who have one or more of the following

risk factors:

• First-degree relative with diabetes

• High-risk race/ethnicity (e.g., African American, Latino, Native American,

Asian American, Pacific Islander)

• History of CVD

• Hypertension (≥140/90 mmHg or on therapy for hypertension)

• HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level

>250 mg/dL (2.82 mmol/L)

• Women with polycystic ovary syndrome

• Physical inactivity

• Other clinical conditions associated with insulin resistance (e.g., severe

obesity, acanthosis nigricans)

2. Patients with prediabetes (A1C ≥5.7% [39 mmol/mol], IGT, or IFG) should be






tested yearly.

3. Women who were diagnosed with GDM should have lifelong testing at least

every 3 years.

4. For all other patients, testing should begin at age 45 years.

5. If results are normal, testing should be repeated at a minimum of 3-year

intervals, with consideration of more frequent testing depending on initial results

and risk status.

6. HIV

**CVD, cardiovascular disease; GDM, gestational diabetes mellitus; IFG, impaired

fasting glucose; IGT, impaired glucose tolerance.

Risk-based screening for type 2 diabetes or prediabetes in asymptomatic children and

adolescents in a clinical setting

Testing should be considered in youth* who have overweight (≥85th percentile) or

obesity (≥95th percentile) A and who have one or more additional risk factors

based on the strength of their association with diabetes:

• Maternal history of diabetes or GDM during the child's gestation A

• Family history of type 2 diabetes in first- or second-degree relative A

• Race/ethnicity (Native American, African American, Latino, Asian American,

Pacific Islander) A

• Signs of insulin resistance or conditions associated with insulin resistance

(acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or

small-for-gestational-age birth weight) B

**GDM, gestational diabetes mellitus.

* After the onset of puberty or after 10 years of age, whichever occurs earlier. If tests

are normal, repeat testing at a minimum of 3-year intervals (or more frequently if

BMI is increasing or risk factor profile deteriorating) is recommended. Reports of

type 2 diabetes before age 10 years exist, and this can be considered with numerous

risk factors.

Criteria defining prediabetes

FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG)

OR

https://care.diabetesjournals.org/content/44/Supplement_1/S15#fn-6






2-h PG during 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0

mmol/L) (IGT)

OR

A1C 5.7–6.4% (39–47 mmol/mol)

**FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired

glucose tolerance; OGTT, oral glucose tolerance test; 2-h PG, 2-h plasma glucose.

Specific types of Diabetes

Cystic Fibrosis–Related Diabetes

Recommendations

Annual screening for cystic fibrosis–related diabetes (CFRD) with an oral glucose

tolerance test should begin by age 10 years in all patients with cystic fibrosis not

previously diagnosed with CFRD. B

A1C is not recommended as a screening test for cystic fibrosis–related diabetes. B

Patients with cystic fibrosis–related diabetes should be treated with insulin to attain

individualized glycemic goals. A

Beginning 5 years after the diagnosis of cystic fibrosis–related diabetes, annual

monitoring for complications of diabetes is recommended

Posttransplantation Diabetes Mellitus

Recommendations

Patients should be screened after organ transplantation for hyperglycemia, with a

formal diagnosis of posttransplantation diabetes mellitus being best made once a

patient is stable on an immunosuppressive regimen and in the absence of an acute

infection. B

The oral glucose tolerance test is the preferred test to make a diagnosis of

posttransplantation diabetes mellitus. B

Immunosuppressive regimens shown to provide the best outcomes for patient and

graft survival should be used, irrespective of posttransplantation diabetes mellitus

risk. E

Monogenic Diabetes Syndromes

Recommendations

All children diagnosed with diabetes in the first 6 months of life should have

immediate genetic testing for neonatal diabetes. A

Children and those diagnosed in early adulthood who have diabetes not characteristic

of type 1 or type 2 diabetes that occurs in successive generations (suggestive of an

autosomal dominant pattern of inheritance) should have genetic testing for maturity-

onset diabetes of the young. A






In both instances, consultation with a center specializing in diabetes genetics is

recommended to understand the significance of these mutations and how best to

approach further evaluation, treatment, and genetic counseling. E

Most common causes of monogenic diabetes

Gene Inheritance Clinical features

MODY

GCK AD

GCK-MODY: stable, nonprogressive

elevated fasting blood glucose;

typically does not require treatment;

microvascular complications are rare;

small rise in 2-h PG level on OGTT

(<54 mg/dL [3 mmol/L])

HNF1A AD

HNF1A-MODY: progressive insulin

secretory defect with presentation in

adolescence or early adulthood;

lowered renal threshold for glucosuria;

large rise in 2-h PG level on OGTT

(>90 mg/dL [5 mmol/L]); sensitive to

sulfonylureas

HNF4A AD

HNF4A-MODY: progressive insulin

secretory defect with presentation in

adolescence or early adulthood; may

have large birth weight and transient

neonatal hypoglycemia; sensitive to

sulfonylureas

HNF1B AD

HNF1B-MODY: developmental renal

disease (typically cystic); genitourinary

abnormalities; atrophy of the pancreas;

hyperuricemia; gout

Neonatal

diabetes

KCNJ11 AD

Permanent or transient: IUGR; possible

developmental delay and seizures;

responsive to sulfonylureas

INS AD Permanent: IUGR; insulin requiring

ABCC8 AD

Permanent or transient: IUGR; rarely

developmental delay; responsive to






Gene Inheritance Clinical features

sulfonylureas

6q24

(PLAGL1,

HYMA1)

AD for

paternal

duplications

Transient: IUGR; macroglossia;

umbilical hernia; mechanisms include

UPD6, paternal duplication or maternal

methylation defect; may be treatable

with medications other than insulin

GATA6 AD

Permanent: pancreatic hypoplasia;

cardiac malformations; pancreatic

exocrine insufficiency; insulin

requiring

EIF2AK3 AR

Permanent: Wolcott-Rallison

syndrome: epiphyseal dysplasia;

pancreatic exocrine insufficiency;

insulin requiring

EIF2B1 AD

Permanent diabetes: can be associated

with fluctuating liver function (138)

FOXP3 X-linked

Permanent: immunodysregulation,

polyendocrinopathy; enteropathy X-

linked (IPEX) syndrome: autoimmune

diabetes, autoimmune thyroid disease,

exfoliative dermatitis; insulin requiring

Pancreatic Diabetes or Diabetes in the Context of Disease of the Exocrine Pancreas

Pancreatic diabetes includes both structural and functional loss of glucose-

normalizing insulin secretion in the context of exocrine pancreatic dysfunction and is

commonly misdiagnosed as type 2 diabetes. Hyperglycemia due to general pancreatic

dysfunction has been called “type 3c diabetes” and, more recently, diabetes in the

context of disease of the exocrine pancreas has been termed pancreoprivic diabetes.

The diverse set of etiologies includes pancreatitis (acute and chronic), trauma or

pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis, fibrocalculous

pancreatopathy, rare genetic disorders, and idiopathic forms, which is the preferred

terminology. A distinguishing feature is concurrent pancreatic exocrine insufficiency

(according to the monoclonal fecal elastase 1 test or direct function tests),

pathological pancreatic imaging (endoscopic ultrasound, MRI, computed

tomography), and absence of type 1 diabetes–associated autoimmunity. There is loss






of both insulin and glucagon secretion and often higher-than-expected insulin

requirements. Risk for microvascular complications is similar to other forms of

diabetes. In the context of pancreatectomy, islet autotransplantation can be done to

retain insulin secretion. In some cases, autotransplant can lead to insulin

independence. In others, it may decrease insulin requirements.

Gestational Diabetes Mellitus

Recommendations

Test for undiagnosed prediabetes and diabetes at the first prenatal visit in those

with risk factors using standard diagnostic criteria. B

Test for gestational diabetes mellitus at 24–28 weeks of gestation in pregnant

women not previously found to have diabetes. A

Test women with gestational diabetes mellitus for prediabetes or diabetes at 4–

12 weeks postpartum, using the 75-g oral glucose tolerance test and clinically

appropriate nonpregnancy diagnostic criteria. B

Women with a history of gestational diabetes mellitus should have lifelong

screening for the development of diabetes or prediabetes at least every 3 years. B

Women with a history of gestational diabetes mellitus found to have

prediabetes should receive intensive lifestyle interventions and/or metformin to

prevent diabetes. A

Screening for and diagnosis of GDM

One-step strategy

Perform a 75-g OGTT, with plasma glucose measurement when patient is

fasting and at 1 and 2 h, at 24–28 weeks of gestation in women not previously

diagnosed with diabetes.

The OGTT should be performed in the morning after an overnight fast of at least

8 h.

The diagnosis of GDM is made when any of the following plasma glucose

values are met or exceeded:

• Fasting: 92 mg/dL (5.1 mmol/L)

• 1 h: 180 mg/dL (10.0 mmol/L)

• 2 h: 153 mg/dL (8.5 mmol/L)

Two-step strategy

Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at






1 h, at 24–28 weeks of gestation in women not previously diagnosed with

diabetes.

If the plasma glucose level measured 1 h after the load is ≥130, 135, or 140

mg/dL (7.2, 7.5, or 7.8 mmol/L, respectively), proceed to a 100-g OGTT.

Step 2: The 100-g OGTT should be performed when the patient is fasting.

The diagnosis of GDM is made when at least two* of the following four plasma

glucose levels (measured fasting and at 1, 2, and 3 h during OGTT) are met or

exceeded (Carpenter-Coustan criteria [193]):

• Fasting: 95 mg/dL (5.3 mmol/L)

• 1 h: 180 mg/dL (10.0 mmol/L)

• 2 h: 155 mg/dL (8.6 mmol/L)

• 3 h: 140 mg/dL (7.8 mmol/L)

Symptoms and signs

Some of the signs and symptoms of type 1 diabetes and type 2 diabetes are:

Increased thirst

Frequent urination

Extreme hunger

Unexplained weight loss

Presence of ketones in the urine (ketones are a byproduct of the breakdown of

muscle and fat that happens when there's not enough available insulin)

Fatigue

Irritability

Blurred vision

Slow-healing sores

Frequent infections, such as gums or skin infections and vaginal infections

Type 1 diabetes can develop at any age, though it often appears during childhood or

adolescence. Type 2 diabetes, the more common type, can develop at any age, though

it's more common in people older than 40.

Complications

Long-term complications of diabetes develop gradually. The longer the patient has

diabetes — and the less controlled his/her blood sugar — the higher the risk of

complications. Eventually, diabetes complications may be disabling or even life-

threatening. Possible complications include:

https://care.diabetesjournals.org/content/44/Supplement_1/S15.figures-only#fn-11






Cardiovascular disease. Diabetes dramatically increases the risk of various

cardiovascular problems, including coronary artery disease with chest pain

(angina), heart attack, stroke and narrowing of arteries (atherosclerosis). If the

patient has diabetes, he/she is more likely to have heart disease or stroke.

Nerve damage (neuropathy). Excess sugar can injure the walls of the tiny

blood vessels (capillaries) that nourish patient`s nerves, especially in his/her

legs. This can cause tingling, numbness, burning or pain that usually begins at

the tips of the toes or fingers and gradually spreads upward.

Left untreated, the patientcould lose all sense of feeling in the affected limbs.

Damage to the nerves related to digestion can cause problems with nausea,

vomiting, diarrhea or constipation. For men, it may lead to erectile dysfunction.

Kidney damage (nephropathy). The kidneys contain millions of tiny blood

vessel clusters (glomeruli) that filter waste from blood. Diabetes can damage this

delicate filtering system. Severe damage can lead to kidney failure or irreversible

end-stage kidney disease, which may require dialysis or a kidney transplant.

Eye damage (retinopathy). Diabetes can damage the blood vessels of the retina

(diabetic retinopathy), potentially leading to blindness. Diabetes also increases

the risk of other serious vision conditions, such as cataracts and glaucoma.

Foot damage. Nerve damage in the feet or poor blood flow to the feet increases

the risk of various foot complications. Left untreated, cuts and blisters can

develop serious infections, which often heal poorly. These infections may

ultimately require toe, foot or leg amputation.

Skin conditions. Diabetes may leave the patientmore susceptible to skin

problems, including bacterial and fungal infections.

Hearing impairment. Hearing problems are more common in people with

diabetes.

Alzheimer's disease. Type 2 diabetes may increase the risk of dementia, such as

Alzheimer's disease. The poorer the blood sugar control, the greater the risk

appears to be. Although there are theories as to how these disorders might be

connected, none has yet been proved.

Depression. Depression symptoms are common in people with type 1 and type 2

diabetes. Depression can affect diabetes management.

Criteriafor the diagnosis of diabetes are any of the following:

An HbA1c level of 6.5% or higher; the test should be performed in a laboratory

using a method that is certified by the National Glycohemoglobin

Standardization Program (NGSP) and standardized or traceable to the Diabetes

Control and Complications Trial (DCCT) reference assay, or

A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher;

fasting is defined as no caloric intake for at least 8 hours, or






A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a

75-g oral glucose tolerance test (OGTT), or

A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient

with classic symptoms of hyperglycemia (ie, polyuria, polydipsia, polyphagia,

weight loss) or hyperglycemic crisis

Questions for the self-control

1. What is Diabetes mellitus?

2. What types of DM do you know?

3. What is the role of glucagon-like peptide in our body?

4. What is the role of Sodium-glucose co-transporter 2 type in our body?

5. Describe the pathophysiological links of type 1 DM

6. Describe the pathophysiological links of type 2 DM

7. What are the criteria of pre-diabetes?

8. What are the criteria of gestation DM?

9. What are the reasons for polyuria?

10. What complication of DM is the most common?

References

1. https://care.diabetesjournals.org/

2. Davidson's Principles and Practice of Medicine, 23rd Edition, 2018.

3. Endocrinology: textbook /Ed. by prof. Petro M. Bodnar.- 4th ed. updated –

Vinnitsa: Nova Knyha, 2017. – 328 р.

4. USMLE Step 2 CK Lecture Notes 2017: Internal Medicine (Kaplan Test Prep). -

2016. - Published by Kaplan Medical. - 474 pages.

5. https://academic.oup.com/ndt/pages/General_Instruction

6. http://www.acc.org/guidelines#sort=%40foriginalz32xpostedz32xdate86069%20d

escending

7. http://www.asco.org/practice-guidelines/quality-guidelines/guidelines

8. https://www.asn-online.org/education/training/fellows/educational-

resources.aspx#Guidelines

9. https://cprguidelines.eu/

10. https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines

11. http://www.eagen.org/

12. http://www.ers-education.org/guidelines.aspx

13. http://www.enp-era-edta.org/#/44/page/home

14. https://www.eular.org/recommendations_management.cfm

15. http://www.esmo.org/Guidelines/Haematological-Malignancies

16. https://ehaweb.org/organization/committees/swg-unit/scientific-working-

groups/structure-and-guidelines/

17. http://www.oxfordmedicaleducation.com/

https://care.diabetesjournals.org/

https://academic.oup.com/ndt/pages/General_Instruction

http://www.acc.org/guidelines#sort=%40foriginalz32xpostedz32xdate86069%20descending

http://www.acc.org/guidelines#sort=%40foriginalz32xpostedz32xdate86069%20descending

http://www.asco.org/practice-guidelines/quality-guidelines/guidelines

https://www.asn-online.org/education/training/fellows/educational-resources.aspx#Guidelines

https://www.asn-online.org/education/training/fellows/educational-resources.aspx#Guidelines

https://cprguidelines.eu/

https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines

http://www.eagen.org/

http://www.ers-education.org/guidelines.aspx

http://www.enp-era-edta.org/#/44/page/home

https://www.eular.org/recommendations_management.cfm

http://www.esmo.org/Guidelines/Haematological-Malignancies

https://ehaweb.org/organization/committees/swg-unit/scientific-working-groups/structure-and-guidelines/

https://ehaweb.org/organization/committees/swg-unit/scientific-working-groups/structure-and-guidelines/

http://www.oxfordmedicaleducation.com/






18. http://professional.heart.org/professional/GuidelinesStatements/UCM_316885_Gu

idelines-Statements.jsp

19. https://www.ueg.eu/guidelines/

20. http://www.diabetes.org

21. http://care.diabetesjournals.org

22. http://www.endocrinology.mif-ua.com

23. https://care.diabetesjournals.org/content/44/Supplement_1/S1

24. https://calgaryguide.ucalgary.ca/pathogenesis-of-diabetes-mellitus-dm-type-ii/

25. https://care.diabetesjournals.org/content/39/2/179.full

26. https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-

20371444

27. https://emedicine.medscape.com/article/117853-overview

http://professional.heart.org/professional/GuidelinesStatements/UCM_316885_Guidelines-Statements.jsp

http://professional.heart.org/professional/GuidelinesStatements/UCM_316885_Guidelines-Statements.jsp

https://www.ueg.eu/guidelines/

http://www.diabetes.org/

http://www.endocrinology.mif-ua.com/

https://care.diabetesjournals.org/content/44/Supplement_1/S1

https://calgaryguide.ucalgary.ca/pathogenesis-of-diabetes-mellitus-dm-type-ii/

https://care.diabetesjournals.org/content/39/2/179.full

https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-20371444

https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-20371444

https://emedicine.medscape.com/article/117853-overview

Documents

ONMedU, Department of Internal medicine 1 with cardio