Type 2 diabetes results from insulin resistance and inadequate insulin secretion. It is characterized by hyperglycemia and increases the risk of microvascular and macrovascular complications if poorly controlled. Treatment involves lifestyle modifications and medications to control blood glucose levels and prevent complications. The goals are to eliminate symptoms, prevent complications, and achieve an A1C under 7%. First line treatment is often metformin, while additional drugs may be added if goals are not met.

1. DIABETES
MELLITUS
TYPE 2

2. INTRODUCTION AND DEFINITION
 Type 2 DM is a chronic disease characterized by hyperglycemia
 Results from a combination of:
• resistance to insulin
• inadequate insulin secretion
• Dysfunctional glucagon secretion
 Poorly controlled type 2 diabetes  an array of microvascular,
macrovascular, and neuropathic complications.

3. CLASSIFICATION
Type 2 DM patients are not absolutely dependent on insulin for life
and are ty pically older than 40 years, hence the older terms
“non–insulin dependent diabetes” and “adult-onset diabetes”.
However;
 many patients with type 2 diabetes are ultimately treated with
insulin
 type 2 diabetes mellitus is occurring at younger ages due to
the epidemic of obesity and inactivity in children and in case of
a family history of diabetes

4. SYMPTOMS
 Many patients with type 2 diabetes are asymptomatic
 Clinical manifestations include the following:
• Polyuria, polydipsia, polyphagia, and weight loss
• Blurred vision
• Lower-extremity paresthesias
• Yeast infections (eg, balanitis in men)

5. RISK FACTORS AND CAUSES
Causes:
• Peripheral insulin resistance
(attributed to elevated levels of free
fatty acids and proinflammatory
cytokines in plasma)
• Beta-cell dysfunction:
inadequate insulin secretion by
pancreatic beta cells
• Hyperglucagonemia and
the consequent hyperglycemia
Diabetogenic lifestyle + Susceptible genotype

6. CONT. CAUSES AND RISK FACTORS
• Obesity
• Age >45
• Family history
• Hispanic, Native American, African American, Asian American, or
Pacific Islander descent
• History of previous impaired glucose tolerance (IGT) or impaired
fasting glucose (IFG)
• Hypertension or dyslipidemia
• History of gestational diabetes
• Polycystic ovarian syndrome
• Genetic influences
• High fasting plasma concentrations of 3 amino acids (isoleucine,
phenylalanine, and tyrosine).

7. DIAGNOSIS AND TESTS
Diagnostic criteria by the American Diabetes Association (ADA):
• Fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or
higher
• 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher
during a 75-g oral glucose tolerance test (OGTT)
• A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in
a patient with classic symptoms of hyperglycemia or hyperglycemic
crisis
• Optional: Hemoglobin A1c (HbA1c) level of 6.5% or higher

8. COMPLICATIONS
Cardiovascular risk * *2-4 times greater in patients with
diabetes* *
1. Lipid abnormalities:
•  small, dense low-density lipoprotein (LDL) cholesterol
•  high-density lipoprotein (HDL) cholesterol
•  triglyceride-rich remnant lipoproteins
2. Thrombotic abnormalities:
• type-1 plasminogen activator inhibitor [PAI-1]
•  fibrinogen
3. Hypertension

9. Cognitive decline
• Hippocampal atrophy
• Temporal, frontal, and limbic gray-matter atrophy
• Frontal and temporal white-matter atrophy
Diabetic retinopathy
End-stage renal disease
Neuropathy and vasculopathy (non-traumatic lower limb amputations )
Cancer (higher risk for bladder cancer )

10. DRUGS AND TREATMENT
Drug class
• Biguanides
• Sulfonylureas
• Meglitinide derivatives
• Alpha-glucosidase inhibitors
• Thiazolidinediones (TZDs)
• Glucagonlike peptide–1 (GLP-1) agonists
• Dipeptidyl peptidase IV (DPP-4) inhibitors
• Selective sodium-glucose transporter-2 (SGLT-2)
inhibitors
• Amylinomimetics
• Bile acid sequestrants
• Dopamine agonists
• Rapid-acting Insulins
• Short-Acting Insulins
• Intermediate-Acting Insulins
• Long-Acting Insulins
Example
• Metformin
• Glimepiride
• Repaglinide
• Acarbose
• Rosiglitazone
• Exenatide
• Sitagliptin
• Canagliflozin
• Pramlintide
• Colesevelam
• Bromocriptine
• Insulin aspart
• Regular insulin
• Insulin NPH
• Insulin detemir
Brand name
• Glucophage
• Amaryl
• Prandin
• Precose
• Avandia
• Byetta
• Januvia
• Invokana
• Symlin
• WelChol
• Cycloset
• NovoLog
• Humulin R
• Humulin N
• Levemir

11. TREATMENT REGIMEN AND GOALS
The goals with diabetes mellitus are to
• eliminate symptoms
• prevent or slow development of complications
Glycemic goals:
 Premeal glucose 80-120 mg/dL,or 100-140 mg/dL for
patients with less stringent glycemic goals
 Therapy should normalize preprandial and
postprandial glycemia
Glycemic monitoring is based on HbA1c + self-monitoring
of blood glucose (SMBG).
 The ACP recommends HbA1c < 7%
 Some organizations recommend HbA1c <6.5%

12. Monotherapy: Metformin is the preferred initial agent for monotherapy and is a standard part of combination
treatments.
Dual-drug therapy: If the patient fails to safely achieve or sustain glycemic goals within 2-3 months
Triple-drug therapy: If 2 drugs prove unsuccessful after 2-3 months

13. NON-PHARMACOLOGICAL
TREATMENT
• Dietary Modifications and Weight loss
• Caloric restriction
• Modest restriction of saturated fats and simple sugars
• Weight loss has been associated with significant
improvements in cardiovascular disease risk factors
Activity Modifications
• Aerobic exercise improves insulin sensitivity and may improve
glycemia markedly in some patients.
• physical activity +dietary modificaions  lower HbA1c
Bariatric Surgery
In morbidly obese patients to:
• improve diabetes control
• in some situations, normalize glucose tolerance.

14. PREVENTION
 To prevent type 2 diabetes mellitus in patients at risk:
• Weight reduction
• Proper nutrition
• Regular physical activity
• Cardiovascular risk factor reduction
• Aggressive treatment of hypertension and dyslipidemia
• Pharmacologic prevention using drugs e.g. Metformin,
Thiazolidinediones, Acarbose
 Stroke Prevention in Diabetes
• Regular blood pressure screening
• Physical activity
• Low-sodium, high-potassium diet
• Blood pressure <130/80 mm Hg
• Drug therapy with ACE inhibitors or ARBs
• Statin therapy

15. BIGUANIDES (METFORMIN)
Mechanism of action
It lowers basal and postprandial plasma glucose levels by:
• decreasing hepatic gluconeogenesis production
• decreasing intestinal absorption of glucose
• improving insulin sensitivity by increasing peripheral glucose
uptake and utilization
 The only oral diabetes drug that reliably facilitates modest
weight loss

16. CONT. BIGUANIDES (METFORMIN)
Side effects, drug interaction, contraindications
• Taken with food to minimize adverse GI effects.
• Contraindicated in patients with impaired renal function (risk
of lactic acidosis)
• Not be used within 48 hours of IV iodinated contrast medium.
Dose and duration of treatment
• Metformin is available in immediate-release and extended-release
formulations, as well as in combination with other antidiabetic
drugs.
• The dose is titrated over 1-2 months to at least 2000 mg daily,
administered in divided doses

17. SULFONYLUREAS
Mechanism of action
• Insulin secretagogues that stimulate insulin release from pancreatic
beta cells and probably
• greatest efficacy for glycemic lowering but effect is only short-term
• May also enhance peripheral sensitivity to insulin secondary to an
increase in insulin receptors or to changes in the events following
insulin-receptor binding.
can usually reduce HbA1c by 1-2% and blood glucose concentrations
by about 20%.

18. CONT. SULFONYLUREAS
Side effects, drug interaction, contraindications
• One study  sulfonylureas were found to be the chief cause of
cardiovascular death in diabetic patients admitted with acute
myocardial infarction
• Induction of weight gain
Dose and duration of treatment

19. MEGLITINIDE DERIVATIVES
Mechanism of action
• much shorter-acting insulin secretagogues than sulfonylureas
Side effects, drug interaction, contraindications
• inducing weight gain as sulfonylureas
• less risk for hypoglycemia than sulfonylureas
Dose and duration of treatment

20. ALPHA-GLUCOSIDASE INHIBITORS
Mechanism of action
• prolong the absorption of carbohydrates
• Thus help prevent postprandial glucose surges.
Side effects, drug interaction, contraindications
induction of flatulence
Dose and duration of treatment