Diabetes mellitus 1

1
Diabetes mellitusPart one Definition,
classification, basic terms

• Oliver Rácz
• In cooperation with
• Marcela Linková (epidemiology)
• Daniela Kuzmová (practical diabetology)
• Lecture from Pathological Physiology
• Safarik University, Medical School, Dept.
  Pathological Physiology, Kosice, Slovakia
• olliracz_at_gmail.com

2
The definition of diabetes mellitus
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.
3
Definition of diabetes mellitus, notes
Diabetes mellitus is a group of metabolic
diseases characterized by hyperglycemia
Diabetes in not one disase but a syndrome of
heterogenous conditions with different
pathogenesis. The disorder of metabolism is not
restricted to sacharides. From practical point of
view all types of diabetes are characterized by
hyperglycaemia. resulting from defects in insulin
secretion, insulin action, or both. Explanation
in part three.
4
The definition of diabetes mellitus, notes
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. Hyperglycaemia in not associated with
pain but in the case of insufficient treatment
diabetic retinopathy, nephropathy, neuropathy and
diabetic foot develop. There is also a
substantial increase of coronary heart disease
risk.
5
Worldwide prevalence and forecast
6
Diabetes A global emergency
Why?
Number of people with diabetes worldwide and per
region in 2017 and 2045 (20-79 years)
NONDIAGNOSED DIABETES (AFRICA, ASIA) OBESITY
!!! AGING OF POPULATION
EUROPE CCA 10 OF ADULT POPULATION INDIA,
CHINA ENORMOUS INCREASE IN THE LAST YEARS
7
Diabetes atlas 2019data not very different from
2018Some details

• In the age group gt 65 years every fifth person
  has diabetes
• 4 from 5 nondiagnosed diabetics live in regions
  with middle and low income and also the mortality
  is the highest there
• 1 from 3 diabetes related death occurs in
  patients aged lt 60 years
• Europe Overall prevalence 8,9 of adult
  population
• Highest absolute numbers Germany, Russia, Turkey
• And in EU near 300 000 children and adolescents
  (more than 30 000 yearly)
• Slovakia 377,5 thousand adults (prevalence 9,1
  ) and 1370 children
• Expenses 1500 eur/year/patient

8
The symptoms of diabetes mellitus

• Other
• Muscle cramps
• Obstipation
• Blurred vision
• Mycotic and bacterial infections

• Basic
• Thirst
• Polyuria
• Sudden loss of body weight
• Fatigue

Most symptoms are not specific. Catchword Think
of it!!!
9
Think of it !!!Before it is too late

• Late diagnosed and treated Type 1

• Nausea, vomitus, abdominal pain
• (acute abdominal condition?)
• Deep breathing, acetone smell
• Kussmaul
• Diabetic ketoacidosis, coma

ALREADY 150 YEARS AGO!
10
Think of it !!!

• Type 2 often and long asymptomatic
• Gestational diabetes mostly asymptomatic

• DANGER
• Acute coronary event, stroke
• HARMFUL
• Both for baby and mother

11
Diagnostic criteria of DMglycaemia

• AN UNAMBIGOUS ALGORHYTM FOR PRACTICE, TWO
  POSSIBILITIES
• Symptoms of DM present, 1 abnormal glycaemia is
  sufficient
• fasting 7.0 mmolL-1 or
• casual 11.1 mmolL-1
• Symptoms of DM absent, for diagnosis 2 abnormal
  values of glycaemia are necessaruz (in two
  consequent days)
• fasting 7.0 mmolL-1 or
• casual 11.1 mmolL-1 or
• 2 hour OGTT value 11.1 mmolL-1

OGTT oral glucose tolerance test, after 75 g
glucose load
12
Diagnostic criteria of DMglycaemia

• AN UNAMBIGOUS ALGORHYTM FOR PRACTICE, BUT SOME
  CAVEATS
• In the everyday medical practice the term
  glycaemia or blood sugar is used. As a matter
  of fact, it is the value of glucose in venous
  plasma mesured in laboratory. The precision of
  the result is secured by quality control and
  standardisation. Glucometer measured values Gare
  not sufficient for diagnosis
• In borderline resulsts one should recognize ths
  uncertainity of measurements and repeat the test
  once more later (not an official statement)
• Is 11.3 mmolL-1 or 6.9 mmolL-1 really 11.3 or
  6.9 ???
• According a German study the uncertainty is 0,44
  mmolL-1 )
• Hb A1c as a diagnostic marker v EU not yet, in
  USA maybe
• DIFFERENTIAL DIAGNOSIS AND MONTORING IS DESCRIBED
  IN PART 5

13
Diagnostic criteria Prediabetes?

• IN ADDITION TO DIAGNOSTIC CRITERIA OF DIABETES
  MELLITUS TWO LABORATORY ABNORMALITIES ARE
  DEFINED. THERE ARE RISK FACTORS OF DIABETES
  DEVELOPMENT (CAN BE CONSIDERED AS PREDIABETES),
  AND ALSO AS A RISK FACTOR OF CORONARY HEART
  DISEASE
• Impaired fasting glycaemia
• (IFG) 6.1 6.9 mmolL-1
• Impaired glucose tolerance
• (PGT) 2 hours after 75 g glucose load 7.8
  11.0 mmolL-1
• in USA from 5.6 mmolL-1
• In Europe the oral glucose tolerance test is
  preferred. It is compulsory to perform in
  gravidity to rule out or confirm gestational
  diabetes mellitus.

14
Prediabetes?Risk factors and screening

• Score systems in general population and
  laboratory measurements in high-risk persons
• Blood glucose in persons gt 45 years, repeat every
  3 years
• In women with gestational diabetes after
  pregnancy
• In obese people regardless on age (including
  children)
• In first degree relatives of diabetics
• In patients with cardiovascular diseases and
  hypertension
• In women with polycystic ovary syndrome
• In patients with AIDS before antiretroviral
  treatment, repeatedly during treatment
• In persons with high probability of insulin
  resistance and/or insufficient insulin secretion
  (haemochromatosis, acanthosis nigricans, cystic
  fibrosis and others (see secondary forms of
  diabetes mellitus)
• In adults with low birth weight and sedentary
  life-style (?) Hard to realize

15
Prediabetes?Risk factors and screening

• ADA scoring sytem
• Age 0 3 points
• Sex men 1, women 0 points
• Hypertension 0 1
• Diabetes in first degree relatives 0 1
• Body mass (norm, overweight, obesity I,II) 0 3
• Physical activity 0 1
• OVER 6 POINTS VISIT AT GENERAL PRACTITIONER AND
  LABORATORY
• It is possible to achieve better score (diet,
  physical activity) without drugs
• A very crude assessment of diabetes risk, but
  useful in general population

16
The definition DM once more and introduction to
classification
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.
17
The proof of two different types of diabetes
mellitus
Bornstein Lawrence, 1951
AGE SEX 32 m 52 f 9 f 28 m 42 m 35 f 47 f 53 f 46 f 57 m
WEIGHT 46 56 25 41 54 79 69 75 85 83
G/ blood 23,9 21,2 22,5 14,9 17,7 16,2 21,2 17,3 17,3 12,9
G/ urine
ketones neg neg neg neg neg
insulin 0 0 0 0 0 0,26 0,29 0,02 0,24 0,20
? ?
18
AGE SEX 32 m 52 f 9 f 28 m 42 m 35 f 47 f 53 f 46 f 57 m
WEIGHT 46 56 25 41 54 79 69 75 85 83
G/ blood 23,9 21,2 22,5 14,9 17,7 16,2 21,2 17,3 17,3 12,9
G/ urine
ketones neg neg neg neg neg
insulin 0 0 0 0 0 0,26 0,29 0,02 0,24 0,20
? ?
AGE AND BODY WEIGHT WERE NOT VERY DIFFERENT BLOOD
GLUCOSE VALUES WERE HIGH IN EACH PROBAND BUT HALF
OF THEM HAD KETONE BODIES IN THE URINE AND NO
INSULIN IN BLOOD (INSULIN MEASURED WITH A
CUMBERSOME METHOD OF GLUCOSE METABOLISM IN
ISOLATED RAD DIAPHRAGMA)
19
Current classification of diabetic syndromesand
their older names

• Type 1 diabetes mellitus
• In the past IDDM or juvenile diabetes
• Type 2 typ diabetes mellitus
• In the past NIDDM or adult diabetes
• Other specific forms of diabetes mellitus
• Gestational diabetes mellitus (temporary
  diagnosis)
• Insulin dependent and Non-insulin dependent

20
Current classification of diabetic
syndromesoccurence and notes

• Type 1 diabetes mellitus, T1DM (5 10 of all
  DM)
• autoimunne (common) and idiopathic (rare)
• Type 2 typ diabetes mellitus, T2DM (near 90 of
  all DM
• Other specific forms of diabetes mellitus
  (relative rare)
• Long list of conditions associated with
  saccharide metabolism disorders and also the
  monogenic forms of diabetes (MODY) are enrolled
  here
• Gestational diabetes mellitus (temporary
  diagnosis)
• Saccharide metabolism disorder manifesting (or
  diagnosed) during pregnancy. After pregnancy
  preclassification in necessary. Pregnancy of a
  diabetic women is not gestational diabetes

21
Other specific forms of diabetes

• GENETIC DEFECTS
• Mody, mitochondrial diabetes, etc.
• GENETIC DEFECTS OF INSULIN EFFECT
• Insulin resistance type A, lipoatrofic diabetes
• DISEASES OF EXOCRINE PANCREAS
• Pancreatitis, tumours, pancreatectomy, cystic
  fibrosis, haemochromatosis
• ENDOCRINOPATHIES
• Cushing syndrome, acromegaly, glucagonoma,
  somatostatinoma, thyreotoxicosis
• DAMAGE CAUSED BY CHEMICAL COMPOUNDS OR DRUGS
• Glucocorticoids, herbicides, antiretroviral
  drugs
• INFECTIONS
• Congenital rubeola, cytomegalovirosis
• RARE IMMUNOLOGICAL CONDITIONS ASSOCIATED WITH
  DIABETES
• OTHER GENETIC CONDITIONS ASSOCIATED WITH DIABETES
• M. Down, Klineferter, Turner, Huntington,
  Prader-Willi

22
Other specific forms of diabetes comments and
an attempt of logical classification

• A Better terminolgy is monogenic forms of
  diabetes. Not very rare and they should be
  considered as a separate group
• Genetic disorders of insulin or insulin receptor
  (B) are extremely rare. On the other side genetic
  polymorphisms are important factors of T2DM
  pathogenesis.
• Groups C and E are secondary conditions due
  to pancreas damage but also the overproduction of
  insulin antagonists (Cushing, acromegaly and
  others gtoup D) belong here.
• Cystic fibrosis and hemochromatosis are
  hereditary diseases, but the damage of endocrine
  pancreas is not the consequence of the genetic
  mutation.
• Some diseases associated with chromosomal
  aberration are associated with diabetic
  syndrome. They also belong to the group of
  genetic forms of DM

23
Alternative classification - ANDIS

• All New Diabetics in Scania (Scandinavia)
• 5800 de novo diagnosed diabetes mellitus patients
• Ahlquist et al., Lancet Diabetes Endocrinology
  2018 Diabetes 2020

1. Classic T2DM 68
2. T2DM with insulin deficiency 10
3. T2DM below age 35 years 6
4. T1DM with absolute insulin deficiency 6
5. T1DM with relative insulin deficiency 5
6. T1DM above age 35 years 2
7. LADA 0,8
8. LADA LIGHT 0,5
9. MODY 0,5
10. SECONDARY FORMS 0,5

A MIXTURE OF OLD AND PATHOGENETIC
CLASSIFICATION Some groups (6,7 and 8) are
questionnable Prediabetes ? Gestational diabetes?
24
Other alternative classification and terminology

• T1DM and LADA, Severe autoimmune diabetes, SAID
• T2DM Severe insulin deficiency diabetes SIDD
• T2DM Severe insulin resistant diabetes, SIRD
• T2DM Mild obesity-related diabetes, MOD
• T2DM mild age-related diabetes, MARD

T1DM LADA as one entity T2DM 4 subgroups, 39
as MARD ?
25
A possible way to future classification
SAID
?
T2DM
SIDD
T1DM
MARD
SIRD
MOD
MODY and monogenic forms
Secondary forms
26
T2DM is a heterogenous disease

• SUBTYPE CLASSIFICATION (T2DMA T2DMG) ???
• ALTERNATIVE SOLUTION (McCarthy, Diabetologia
  2017)
• Pigeonholes or a painters palette?
• Weighted assessment of T2DM pathogenesis factors!

27
Component analysis of factors responsible for
T2DM development
28
Component analysis of factors responsible for
T2DM development
A REAL PERSPECTIVE It is an urgent need to find
components (in addition to weight, age, familiar
background) of the disease development. Research
of metabolic disorder biomarkers can solve it.