The document provides a comprehensive overview of diabetes, including its definitions, classifications, symptoms, and diagnostic criteria. It outlines the differences between type 1 and type 2 diabetes, their underlying pathophysiology, and the importance of insulin secretion and action in managing the disease. Additionally, it discusses complications associated with diabetes and treatment options, emphasizing the importance of glycemic control in preventing long-term damage to organs.

1. APPROACHTO DM
Professor/ Mohammed Ahmed Bamashmos
Professor of internal medicine and endocrinology
Faculty of medicine Sanaa University

2. Defination
Diabetes 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 differentorgans, especially the eyes, kidneys,
nerves, heart, and blood vessels.The degree of hyperglycemia (if any) may change over time,
depending on the extent of the underlying disease process .A disease process may be present but
may not have progressed far enough to cause hyperglycemia.The same disease process can cause
impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) without fulfilling the criteria
for the diagnosis of diabetes. In some individuals with diabetes, adequate glycemic control can be
achieved with weight reduction, exercise, and/or oral glucose-lowering agents.These individuals
therefore do not require insulin.Other individuals who have some residual insulin secretion but
require exogenous insulin for adequate glycemic control can survive without it. Individuals with
extensive β-cell destruction and therefore no residual insulin secretion require insulin for survival.
The severity of the metabolic abnormality can progress, regress, or stay the same.Thus, the
degree of hyperglycemia reflects the severity of the underlying metabolic process and its
treatment more than the nature of the process itself.

3. classification

4. Diabetes can be classified into the following general categories:
1. Type 1 diabetes (due to autoimmune b-cell destruction, usually leading to ab- solute insulin
deficiency, including latent autoimmune diabetes of adulthood)
2. Type 2 diabetes (due to a non-autoimmune progressive loss of adequate b-cell insulin
secretion frequently on the background of insulin resistance and metabolic syndrome)
3. Specific types of diabetes due to other causes, e.g., monogenic diabetes syn- dromes (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 treat- ment of HIV/AIDS, or
after organ transplantation)
4. Gestational diabetes mellitus (diabetes diagnosed in the second or third tri- mester of
pregnancy that was not clearly overt diabetes prior to gestation)

5. SYMPTOMS
1- Classic symptoms of hyperglycemia include polyuria, polydipsia, nocturia, blurred vision and, infrequently, weight
loss. These symptoms are often noted only in retrospect, after a blood glucose value has been shown to be elevated.
Polyuria occurs when the serum glucose concentration rises significantly above 180 mg/dL (10 mmol/L), exceeding the
renal threshold for glucose, which leads to increased urinary glucose excretion. Glycosuria causes osmotic diuresis (ie,
polyuria) and hypovolemia, which in turn can lead to polydipsia. Patients who replete their volume losses with
concentrated sugar drinks, such as non-diet sodas, exacerbate their hyperglycemia and osmotic diuresis.
2- Acute complication as - Diabetic ketoacidosis ( 20% of patients with type 1diabetes) - Rarely adults with type 2
diabetes can present with a hyperosmolar hyperglycemic state, characterized by marked hyperglycemia without
ketoacidosis, severe dehydration, and obtundation. Diabetic ketoacidosis (DKA) as the presenting symptom of type 2
diabetes is also uncommon in adults but may occur under certain circumstances (usually severe infection or other
illness) and in non-Caucasian ethnic groups.
3- Chronic complication Among patients with type 2 diabetes in the United Kingdom Prospective Diabetes Study,
25% had retinopathy; 9%, neuropathy; and 8%, nephropathy at the time of diagnosis.
4- Asymptomatic ;in older studies, the typical patient with type 2 diabetes had diabetes for at least 4-7 years at the time
of diagnosis. 5- Atypical presentation ; Presentation of diabetes in elderly is less classical. Index of suspicion has to be
high as patients usually do not develop glycosuria (increased renal threshold) and polydipsia (impaired thirst
mechanism). They may present with non-specific features (failure to thrive, falls, dizziness, confusion, nocturia, etc)
and Non Ketotic Hyperosmolar State (NKHS) . They may also present with infectious complications like malignant
otitis externa, septicaemia, diabetic foot and complicated renal infections

6. Diagnosis
1- Is the patients has diabetes ; - If there is any symptom or sign suggest DM
Order for one or more the following tests to diagnose DM
1- HbA1C. FBS , RBS ,GTT
2- Other tests to be ordered as needed ( serum insulin , C-peptide , autoantibodies ,
HOMA-IR, genes )
Interpretation of the results ;

8. Criteria for diagnosis

9. advantage and disadvantage of test

10. Which types of diabetes that patients has
1-Type 1 diabetes
- Clinical supports ; a- Age ; usually young but may present in middle or old as (LADA) b- Family history ; less frequent c-
Duration of illness , short d- Onset is progressive and may present with acute complication e- Body weight ; normal
- - Laboratory support ;
- a-Assessment of beta cell function ;
Method used to assess beta cells function
1- Serum insulin level ;
Disadvantage ;
a- It has short half life
b- 30% undergo hepatic clearance
c- Its measurement is interfered with exogenous insulin by RIA
2- C-peptide - Plasma C-peptide - Urine creatinine to C-peptide ratio Advantages ;
a- Long half life
b- No hepatic clearance
c- No interference with exogenous insulin 3- HOMA-B-cell

11. B- presence of autoantibodies
- types

12. importance ;
- diagnosis
- subtype of type 1 ;

13. - for staging

14. 2-Type 2 diabetes
- 1- Clinical supports
- a- Age ; usually middle and old but may present in children and adult as (type 2 diabetes of youth )
- b- Family history ; more frequent
- c- Duration of illness , long
- d- Onset is slow progressive and may present with chronic complication
- e- Body weight ; usually obese
- - 2- Laboratory support ;
- A- assessment of IR
- B- Assessment of beta cell function ; 1- Serum insulin 2- Serum C-peptide level

15. 3-Latent autoimmune diabetes of adult(LADA) ;
1- Clinical support
a- Age ; usually 45-70 years
b-Family history ; more frequent
c - Duration of illness , long
d- Onset is slow progressive and may present with chronic complication
e- Body weight ; usually normal
2- Laboratory support ;
a- Assessment of beta cell function ; 1- Serum insulin ; low 2- Serum C-peptide level ; low
b-The presence of autoantibodies ; positive

16. 4-Type 2 diabetes of youth
1- Clinical support ;
a- Age ; 12-18 y
b- Family history ; positive
c- Onset ; slow , about is asymptomatic
d- Duration ; long e- Over weight
f- Ethenic variation
g- Feature of insulin resistance ; as acanthosis negrecans , hypertension , POS , dyslipidemia h- History of GDM
2- Laboratory support ;
- a- Assessment of beta cell function ; 1- Serum insulin ; normal 2- Serum C- peptide ; normal
- b- No auto antibodies

18. 5-Ketosis prone type 2 DM
1-Sudden in onset
2-No obesity
3-Positive FH
4-May present with DKA
5-Absence of markers of autoimmunity
6-No insulin resistance
7-There is decrease in first phase insulin secretion

19. 6- MONOGENIC DIABETES
A- neonatal
B- MODY

20. 7-Diagnosis of GDM

21. TYPE 1 DM
Defination ;
Prevalence ;
Pathogenesis ;

23. Natural history

24. Staging

25. Subtype of type 1
1- Acute
• 2- slowely progressive

26. diagnosis
A- clinical
B- laboratory
1- Presence of autoantibodies
importance
2- assessment of beta cell function

27. Prevention

28. treatment
1- treatment target
- Blood glucose
- - FBS
- - RBS
- - HbA1C
- -

29. • treatment types
• A- diet

30. Treatment type
1- insulin
- According to source
- A - human insulin ;
- - SHORT ACTING ;
- - soluble
- - intermediate acting
- - NBH
- - long acting
- ultralente
- B- insulin analogue
- - rapid acting
- - aspart
- - lispro
- - glargine

31. long acting ;
- glargine
- detemer

32. according to onset and duration

33. who the pancreas secreate insulin
• basal insulin secretion ( 1iu|hr ) its aim is to suppress glycogenolysis , lipolysis and proteolysis
• Meal related insulin secretion as following ( 4 iu before breakfast , 3iu before lunch , 6 iu before dinner , 2 iu at bed time
snack )
• PHASESOF INSULIN SECRETION
• In nondiabetic individuals, approximately 50% of the total daily insulin is secreted during basal periods, suppressing
lipolysis, proteolysis, and glycogenolysis.The remainder of insulin secretion is postprandial. In response to a meal, there
is a rapid and sizable release of preformed insulin from storage granules within the beta cell.This "first phase" of insulin
secretion promotes peripheral utilization of the prandial nutrient load, suppresses hepatic glucose production, and limits
postprandial glucose elevation. First-phase insulin secretion begins within 2 minutes of nutrient ingestion and continues
for 10 to 15 minutes.The second phase of prandial insulin secretion follows, and is sustained until normoglycemia is
restored.
• First-phase insulin secretion is often represented in clinical studies by the acute insulin response to an intravenous
glucose bolus.While an intravenous glucose bolus is not equivalent to an oral mixed meal, it serves as a standardized
beta-cell stimulus by which first-phase insulin secretion can be carefully compared among different subjects. Further, it
demonstrates the sensitivity to and insulin response of the beta cell specifically to the glucose stimulus. It is this loss of
beta-cell glucose sensitivity and responsiveness that declines early in the development of type 2 diabetes, even while
responses to amino acid and other stimuli are preserved.
• Evidence of impaired first-phase insulin release can be seen in the glucose tolerance test, demonstrated by a
substantially elevated blood glucose level at 30 minutes, a marked drop by 60 minutes, and a steady climb back to
baseline levels over the following hourly time points

34. dose of insulin ;
- dose of insulin
0.5-1 iu/kg / day
Higher amount is required during
- puberty
- pregnancy
- medical illness
half of the total dose is given as basal insulin and half as prandial
Method ;
1- multidose regimen ;

40. drugs used in type 1 DM ;
- Amylin analogues ;
- Mechanism of action ;
-

41. Pramlintide is based on the naturally occurring b-cell peptide amylin and is approved for use in adults with
type 1 diabetes. Clinical trials have demonstrated a modest reduction in A1C (0.3–0.4%) and modest weight
loss (1 kg) with pramlintide
2- metformin
3- GLP1RA ; Liraglutide
dose ; 1.8mg /day
advantage ;
- decrease HbA1C
- decrease body weight
- reduction in insulin dose
4- SGLT2I

42. Type 2 DM
Definition ;
This form of diabetes, which accounts for ∼90–95% of those with diabetes, previously referred to as non-insulin-
dependent diabetes, type II diabetes, or adultonset diabetes, encompasses individuals who have insulin resistance
and usually have relative (rather than absolute) insulin deficiencyAt least initially, and often throughout their
lifetime, these individuals do not need insulin treatment to survive
Pathogenesis ;
1- Insulin resistance
2- Decreased insulin secretion by beta cells
3- Increased glucose production by liver
4- Incretin hormones deficiency and resistance
5- Increased renal tubular reabsorption of glucose
6- Hyperglucogenemia
7- Amylin deficiency
8- Rule of CNS

44. 1- insulin resistance ;
Defination ; Definition ; Insulin resistance (IR) is a physiological condition in which cells fail to
respond to the normal actions of the hormone insulin.The body produces insulin, but the cells in
the body become resistant to insulin and are unable to use it as effectively, leading to
hyperglycemia. Beta cells in the pancreas subsequently increase their production of insulin,
further contributing to hyperinsulinemia
Causes ;
rule of obesity in IR

46. • site of insulin resistance ‘Sites ;
• a- Liver ; normally insulin suppress the hepatic glucose production , in case of insulin resistance the glucose production by
liver is increased leadind to fasting hyperglycemia
• b- skeletal muscle ; its important for oxidation and storage of glucose as glycogen in insulin resistance thereis defect in
both uptake and storage of glucose ; which is due to ;
• -defect in the upregulation of GLUT 4
• - Increased FFA flux to the skeletal muscle leads to inhibition of muscle glucose uptake ( Randle hypothesis ) , FFA inhibit
muscle glucose utilization by inhibiting phosphofructokinase leading to increased muscle glucose with decreased uptake
–
• c- adipose tissue ; insulin resistance at adipose tissue leads to increased activity of enzyme lipoprotein lipase this leads to
increase FFA production which in turn leads to
• - Insulin resistance at liver
• -Insulin resistance at skeletal muscle
• - Deposition in beta cells of pancrease leads to decreased insulin secretion

47. Sequale of IR

48. 2-Beta cells dysfunction ;
Causes ;

49. • 3-Incretin deficiency and resistance
• Incretins are a group of gastrointestinal hormones that cause an increase in the amount
• of insulin released from the beta cells of the islets of Langerhans after eating, before blood
glucose levels become elevate d.They also slow the rate of absorption of nutrients into the
blood stream by reducing gastric emptying and may directly reduce food intake. As expected,
they also inhibit glucagon release from the alpha cells of the Islets of Langerhans.The two
main candidate molecules that fulfill criteria for an incretin are glucagon-like peptide-1 (GLP-
1) and gastric inhibitory peptide (also known as: glucose-dependent insulinotropic
polypeptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl
peptidase-4 (DPP-4).
•

51. 4- Rules of the kidney Rules of kidneys:Sodium-dependent glucose cotransporters (or
sodium-glucose linked transporter, SGLT) are a family of glucose transporter found in the
intestinal mucosa(enterocytes of the small intestine (SGLT1) and the proximal tubule of
the nephron (SGLT2 in PCT and SGLT1 in DCT).They contribute to renal glucose
reabsorption. In the kidneys, 100% of the filtered glucose in the glomerulus has to be
reabsorbed along the nephron (98% in PCT, via SGLT2). In type 2 diabetes there is
increased glucose reabsorption by the kidneys .

52. 5- Amylin hormone affect the rate of postprandial glucose appearance through a variety
of mechanisms: — - CNS-mediated (hypothalamic) mediated anorectic effects
todecrease food intake; mediated by stimulation of central amylin receptors, which are
different from the receptors mediating the anorectic effects of GLP-1 — - slows gastric
emptying due to activation of amylin receptors located in the nucleus accumbens &
dorsal vagal complex of the CNS.This increases parasympathetic (vagal) stimulation of
the GI tract, resulting in depressed GI motility & slowing of gastric emptying (Ryan et al,
2005) — -suppresses glucagon secretion from pancreatic α cells by a neuroendocrine
pathway that is not well understood; this results in suppression of endogenous glucose
output from the liver (Ryan et al, 2005)

53. • 6-Rule of central nerve system
• In type 2 DM early morning dopamine level is increased this leads to
• increased hhypothalamic CNS activity increased hepatic glucose production increased lipolysis and FFA increased
lipogenesis andTG
• all these changes leads to
• glucose intolerance
• insulin resistance
• dyslipidemia
• CVD
•

55. • 7-Increased glucagon secretion by pancrease
• glucagon had been discovered earlier than insulin, T2DM would well be defined as a state of hyperglucagonemia resulting in
hyperglycemia due to glucagon-induced hepatic gluconeogenesis. Hyperglucagonemia is a characteristic of bothT1DM and T2DM.
Unger RH (1971,27 1974,28 197729) has discussed the role of pancreatic islet a and b cell inter-relationship in health and disease
and the role of glucogon in diabetes. The normal reciprocal response of insulin and glucagon regulates postprandial glucose levels.
Impaired a cell regulation leads to excessive glucagon release in the fasting and post-prandial state, with increase hepatic glucose
production (HGP) and hyperglycaemia

56. Natural history

57. Staging

58. Diagnosis
1- clinical
2- investigation
- to diagnose DM
- for screening in asymptomatic

59. for DD
- PRESENCE OF AUTOANTIBODIES
- Assessment of IR ;
IMPORTANCE ;
- staging of type 2DM
-
-

60. For subtype of type 2 DM
For chocing proper treatment
3- Assessment of beta cell function
importance

61. Treatment
treatment goal

62. treatment types ;
1- exercise

64. Drugs
Who to choice

65. Types

66. • Mechanism of action

67. Safty profile ;