L2: Managment of DM Flashcards
Goals of TTT of DM
Target of TTT in DM
- Normal glucose levels
- Weight Loss
- Improve blood lipid profile
- Lower blood pressure
what are glycemic targets?
- HbA1C < 7 %
- Fasting blood glucose 80 - 130 mg/dL
- Postprandial blood glucose < 180 mg/dL
Weigth target in DM
- Body mass index <25 kg/m2
- Waist : hip ratio men <0.95 - women <0.8
what is Diabetes Remission?
Return of HbA1c <6.5%
Characters of Diabetes Remission
- Spontaneously or following intervention
- Persist for 3 months
- In absence of glucose lowering pharmacotherapy
Lipid profile targets in DM
Blood Pressure target in DM
130/80 mmHg (but depends on age, diabetes duration, complication risk)
Aspects of Therapeutic Lifestyle Modification in DM
- Weight loss (for overweight and obese patients)
- Physical Activity
- Diet
Weight loss
(Therapeutic Lifestyle Modification)
Reduce by 5% to 10%
Physical activity
(Therapeutic Lifestyle Modification)
150 min/week of moderate-intensity exercise (e.g., brisk walking) plus flexibility and strength training.
Diet
(Therapeutic Lifestyle Modification)
CHO eating in DM
healthful carbohydrates (fresh fruits and vegetables, legumes, whole grains)
Fat Eating in DM
- Healthful fats → containing polyunsaturated fatty acids (nuts, avocado, certain plant oils, fish)
- Limit saturated fats → (butter, fatty red meats, tropical plant oils, fast foods) and trans fat
Protein Eating in DM
- Consume protein in foods with low saturated fats (fish, egg whites, beans)
- there is → no need to avoid animal protein
- Avoid or limit processed meats
Micronutrients in DM
- Routine supplementation is not necessary → a healthful eating meal plan can generally provide sufficient micronutrients
- Vitamin supplements → recommended to patients at risk of insufficiency or deficiency
However, Vit B is good for neuropathy associated with DM
What are Categories of Oral Hypoglycemic Agents?
Insulin Sensitizers
- Biguanides (Metformin)
- Thiazolidinedione (TZDs)
Insulin Secretagogues
- Sulphonylurea ( Long acting secretagogues )
- Non-Sulphonylurea secretagogues ( Glinides ) ( Short acting secretagogues )
- Glucagon like peptide 1 receptors agonists ( GLP1 agonists ) (Injectable)
- Dipeptidyl peptidase-4 inhibitors ( DPP4 inhibitors )
what is an example of Alpha-glucosidase inhibitors?
(Acarbose)
what is the corner stone in treatment of type 2 diabetes in all guidelines?
Metformin
MOA of different Oral Hypoglycemic Agents
MOA of Metformin
What is an example of Biguanides?
Metformin
Advantages of Metformin
Cheap
No weight gain
No episodes of hypoglycemia
Beneficial cardiovascular outcomes
SE of Metformin
- Gastro-intestinal → like flatulence and diarrhea
- Fatal lactic acidosis. → rarely
CI of Metformin
- diabetic patients with renal and/or hepatic disease
- diabetic ketoacidosis
Dose of Metformin
- Starting dose : 500 mg taken once daily with breakfast for one week
- Up-titration of the dose should be continued as required
- Maximum: 2 g per day.
when not to give Metformin (GFR)?
if the estimated glomerular filtration rate (eGFR) is <30 ml/min/1.73 m2.
Members of Thiazolidinediaones
Pioglitazone → 15- 45 mg/day & Rosiglitazone
MOA of Thiazolidinediaones
Advantages of Thiazolidinediaones
No or minimal hypoglycemia
Expected HbA1c change (%) → 0.5 – 1.4
Improves lipid profile
SE of Thiazolidinediaones
1) Weight gain
2) Edema both L.L
3) Osteoporosis especially in postmenopausal females.
CI of Thiazolidinediaones
1) Pregnancy
2) Advanced heart failure
3) Hepatic cell failure
4) Renal failure
5) Risk of bladder cancer
what type of secretagogues are Sulfonylureas?
Long acting
Examples of Sulfonylureas
MOA of Sulfonylureas
Advantages of Sulfonylureas
- Expected HbA1c change (%)→ 1.0 – 2.0 ( Effective reduction of HA1C )
- Rapidly effective
- ↓ Microvascular risk
- Not Expensive
SE of Sulfonylureas
- Hypoglycemia
- Weight gain
- Blunting of myocardial ischemia
CI of Sulfonylureas
Pregnancy
Type 1 diabetes.
Patients with acute or end-stage liver disease
Patients with end-stage renal diseases
what type of secretagogues are Glinides?
Short-Acting
Members of Glinides
Natiglinide & Mitiglinides & Repaglinide
what are Glinides Called?
They are called prandial glucose regulators as these drugs act mainly on the postprandial glucose excursions
MOA of Glinides
- Act on the same potassium channels of Sulphonylurea.
- Enhance insulin secretion
SE of Glinides
Hypoglycemia
Weight gain
Explain Enteroinsular axis
What are members of GLP1 Agonists?
Liraglutide/d
Dulaglutide/w
Semaglutide/w
Lixisinatide/d
Method of adminstration of GLP1 Agonists
Injectable
Advantages of GLP1 Agonists
1) No hypoglycemia
2) Weight loss
3) Cardiovascular & renal protection.
Disadvantages of GLP1 Agonists
Costy.
Subcutaneous injection
SE of GLP1 Agonists
- GIT upset ( Diarrhea - Nausea & vomiting )
- Acute pancreatitis
what are members of DPP4 Inhibitors?
1) Sitagliptin & Linagliptin
2) Alogliptin & Saxagliptin.
3) Vildagliptin
MOA of DPP4 Inhibitors
- ↓destruction of endogenous GLP-1 (glucagon like polypeptide 1)
- ↑↑ Incretin level which → stimulates insulin release from pancreatic B-cells in a glucose dependent manner.
Advantages of DPP4 Inhibitors
No hypoglycemia
No weight gain
Well tolerated drugs.
Disadvantages of DPP4 Inhibitors
- Costy.
- Expected HbA1c change (%)→ 0.6 – 0.9
SE of DPP4 Inhibitors
Alter Immune function
- Increased upper respiratory infection → nasopharyngitis, headache and nausea
- Angioedema/urticaria
MOA of Alpha Glucosidase Inhibitors
- ↓↓ The upper gastrointestinal enzymes that convert dietary starch and other
complexes into simple sugar which can be absorbed. - Mild to moderate reduction in postprandial glucose.
Advantages of Alpha Glucosidase Inhibitors
no hypoglycemia
no weight gain
SE of Alpha Glucosidase Inhibitors
Usually cause flatulence and diarrhea
What are members of Sodium Glucose Co-Transporter 2 Inhibitors?
Canagliflozin
Dapagliflozin
Empaglifiozin
MOA of SGLT2 Inhibitors
- Inhibits glucose re-absorption from proximal convoluted tubules of the kidney
(Reduce renal glucose reabsorption by 30–50%) - Their glycemic efficacy is dependent on glomerular filtration, and they are less
efficacious in renal impairment.
Advantages of SGLT2 Inhibitors
No hypoglycemia
Mild reduction in systolic blood pressure
Decrease body weight
↓ Albuminuria
Improve lipid profile
Disadvantages of SGLT2 Inhibitors
- Expensive drugs
- Mild to moderate reduction in A1C → 0.6 – 0.9
SE of SGLT2 Inhibitors
Urinary-tract infections
Ketoacidosis
Hypotension
Acute kidney injury
when not to use dapagliflozin? (GFR)
if GFR is less than 60
MOA of Insulin
Introduction to insulin
- Peptide hormone composed of 51 amino acids that is synthesized, packaged, and secreted in pancreatic beta cells.
- Insulin therapy is appropriate for patients with type 1 & type 2 diabetes.
- The absolute insulin deficiency of established type 1 diabetes can only be treated effectively with multiple daily insulin injections
..
Indications of Insulin
(CI of Sulfunylureas)
Insulin therapy is often used early for type 2 diabetes patients, who are: ……
- Highly symptomatic with marked catabolic state
- Newly diagnosed with very high glucose level
SE of Insulin
- Hypoglycemia & hypoglycemic coma
- Weight gain & edema
- Injection site problems
- Insulin allergy and hypersensitivity
Levels of Hypoglycemia
Clinical Manifestations in Hypoglycemia
TTT of Hypoglycemia
what causes Weight gain & edema in insulin therapy?
Due to lipogenesis and salt & water retention
Injection site problems in insulin
- Fat hypertrophy (“lipohypertrophy”) appears as soft lumps at the injection sites.
- Fat atrophy (“lipoatrophy”) is a loss of fat under the skin’s surface.
- Scarring of the fat (“lipodystrophy”) is caused when you inject too many times into the same site treated by frequent change of sites of injection
Insulin allergy and hypersensitivity
- Rare
- Result from the insulin molecule itself, and also from protamine
- Self-limited OR systemic reactions ( urticaria or anaphylaxis )
TTT of Insulin allergy and hypersensitivity
- Using a continuous subcutaneous pump infusion of insulin
- Switching from human insulin to insulin analogues such as aspart or lispro.
Def of Insulin Resistance
- ↑↑ daily insulin requirements > 200 IU in absence of conditions associated with ↑↑ insulin demand (infection –pregnancy…)
Cause of Insulin Resistance
- Obesity: commonest cause for mild resistance & Antibodies against insulin preparations OR receptors
Explain Somogyi Effect
(Pseudo-insulin resistance)
- Nocturnal hypoglycemia (known by night mare & sweating of the patient & morning headache) ——> Increased hyperglycemic hormones —-> morning hyperglycemia
Cause of Somogyi Effect
occurs due to high dose of night insulin or low amount of dinner
TTT of Somogyi Effect
treated by reduction of night insulin
Dawn Phenomenon
Rapid acting Insulin Preparations
Short acting Insulin Preparations
Intermediate acting Insulin Preparations
Long acting Insulin Preparations
Insulin Mixutres
- Humulin 70/30
- Mixtard 70/30
NovoMix 30
Routes of Adminstration of Insulin
How you calculate the dose of insulin?
When initiating insulin therapy, base line total daily dose is often calculated as 0.6 X body weight in kilograms
Insulin regimen 1 (Twice Daily)
Insulin regimen 2 (Basal Bolus)
Selecting initial insulin regimen based on blood sugar profile
Initiating with Basal insulin
Initiating with premixed insulin
Initiating with prandial insulin
Initiating with Basal-bolus insulin
Done
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