Diabetes Milletus Flashcards
- Most common endocrine disorder
Diabetes Mellitus
- Chronic condition
Diabetes Mellitus
- A group of metabolic disease
characterized by inappropriate
chronic hyperglycemia with
disturbances of carbohydrates, fats and protein metabolism resulting from defect in insulin secretion, insulin action or both
Diabetes Mellitus
- Infantile or
Childhood - Young
- Adult
- Elderly
1965
- Insulin
dependent DM - Non-Insulin
Dependent DM - Other Types
1985
- type 1
- type 2
1999
- type 1
- type 2
- specific type due to other causes
- gestational diabetes
2023
- Destruction of pancreatic beta cell
responsible of insulin production - Associated with autoimmune disease
- Usually develops in children and
young adult - Associated with a faster onset of
symptoms, leading to dependency on
extrinsic insulin for survival
type 1 DM
- More common type of diabetes
- Occurs in adults older than 40 years
- Peaks onset between 60 and 70
years - Caused by a relative insulin
deficiency and the body’s inability to
effectively use insulin - Symptoms are slower in onset and
less marked than those of Type 1 DM
Type 2 DM
- Hyperglycemia that is first detected during pregnancy, usually
diagnosed during the 2nd or 3rd trimester
Gestational diabetes
- Hyperglycemia in pregnancy is associated with adverse
outcomes, including hypertension or pre-eclampsia, fetal
macrosomia or fetal death
Gestational diabetes
adverse outcomes from hyperglycemia in pregnancy
pre-eclampsia, fetal macrosomia, fetal death
Diabetes is a result of a pre-existing condition
Specific Type due to other causes
Acute, symptomatic
Type 1 DM
Slow, often asymptomatic; symptoms occur when condition is already chronic
Type 2 DM
Weight loss, polyuria,
polydipsia, polyphagia
Type 1 DM
If symptomatic, similar with T1DM + obese, strong family history of T2DM, PCOS
Type 2 DM
body burns fat for energy instead of glucose
ketosis
Ketosis: Almost always present
Type 1 DM
Ketosis: Usually absent
Type 2 DM
Biomarker that indicates how much insulin your body has
C-peptide
C-peptide: Low or absent
Type 1 DM
C-peptide: Normal or elevated
Type 2 DM
Antibodies
- Positive: Islet Cell Antibodies
(ICA), ICA 512, Anti-Glutamic
Acid Decarboxylase (Anti-GAD)
Type 1 DM
Antibodies
- Negative: Islet Cell Antibodies (ICA), ICA 512, Anti-Glutamic Acid Decarboxylase
(Anti-GAD)
Type 2 DM
Insulin
Type 1 DM
Lifestyle modification, Oral anti-diabetic agents, Insulin
Type 2 DM
Associated auto-immune
diseases: yes
Type 1 DM
Associated auto-immune
diseases: No
Type 2 DM
Glucose enters the cell via theGLUT 2 transporter → glycolysis → ATP (by product) will bind to ATP sensitive K-channels →K-channel will close, preventing K efflux → depolarization due to increased K → signal Ca channel to open → entry of Ca inside cell→ stimulation of insulin production through a vesicle → bloodstream
main pathway
Glutamic acid -> Glutamic acid decarboxylase -> GABA -> insulin
alternative pathway
inhibits formation of GABA and will lead to Type 1 DM
Anti-GAD antibodies
Hormones affecting sugar
levels in the body
- insulin
- counterregulatory hormones
- incretin hormones
- amylin
Regulates CHO, CHON and
lipid metabolism by
promoting glucose uptake
into the cell
Insulin
Promotes conversion of
glucose to glycogen
Insulin
Facilitates cellular uptake of
amino acids
Insulin
Decreases the breakdown of
fatty acids into ketone bodies
insulin
Produced during low glucose
levels to increase the amount
of glucose in the body
Counterregulatory hormones
Antagonizes insulin effects
Counterregulatory hormones
Promotes conversion of
glycogen to glucose
Counterregulatory hormones
glucagon, growth hormones,
catecholamines, cortisol
Counterregulatory hormones
Released or secreted after
meal or nutrient intake to
stimulate release of insulin
incretin
Inhibits inappropriate glucone
secretion and increases beta
cell growth and reproduction
incretin
Suppresses appetite
incretin
Gastric inhibitory peptide
(GIP) and Glucagon-like
peptides (GLP)
incretin
Co-secreted with insulin
amylin
Lowers post-prandial blood
glucose level by prolonging
the gastric emptying time
amylin
Reduces post-prandial
glucagon secretion
amylin
Suppresses appetite
(2)
amylin
Human Leukocyte Antigen (HLA) DQA
and DQB appear to code for either
disease susceptibility or resistance
T1DM Genetics
Viral, chemical or dietary
T1DM environment
Assigns if person is susceptible or resistant to DM
DQA and DQB
- Anti-insulin ,anti-beta cell antibodies
- Antibodies to glutamic acid
decarboxylase
T1DM autoimmunity
> 90% concordance rate in identical twins if one has _______
T2DM genetics
Improper insulin secretion
T2DM Beta cell dysfunction
Post-receptor binding, a decreased number of insulin receptor or defects in insulin receptors can lead to hyperglycemia
T2DM peripheral site defect
Risk factors for diabetes
- overweight or obesity (+)
- Maternal history of DM or GDM during the child’s gestation
- Family history of T2 DM in first- or second-degree relative
- Race/ethnicity (Native American, African American, Latino, Asian American, Pacific Islander)
- Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, HTN, dyslipidemia, PCOS, or small-for-gestational-age birth weight)
- Glucosuria
- Polyuria
- Polydipsia
- Polyphagia
- Weight loss
Most common clinical manifestations
≥ 126 mg/dL
Fasting Blood Glucose Level
≥ 200mg/dL
Random Blood Glucose Level/ Oral Glucose Tolerance Test
≥ 6.5%
Hemoglobin A1c
- Atherosclerosis
>Stroke, Heart Attack, Artery Disease - Retinopathy
>Cataract, Glaucoma - Neuropathy
>Diabetic Foot, nerve endings - Nephropathy
> liver, nephron damage
Complications associated with Diabetes
acanthosis nigricans, HTN, dyslipidemia, PCOS, or small-for-gestational-age birth weight
Clinical conditions with Insulin resistance
- Prevent Complications
- Optimize Quality of Life
Treatment goals
< 7.0%
A1C - glycemic recommendations for many nonpregnant adults with diabetes
80 - 130 mg/dl
pre prandial CPG - glycemic recommendations for many nonpregnant adults with diabetes
<180 mg/dl
peak post-prandial CPG (1-2 hours after meal) - glycemic recommendations for many nonpregnant adults with diabetes
- Required for glycemic management in individuals with T1DM
- May be used in combination with oral agent or amylin agonist
- May also be initial or adjunctive agent for individual with T2DM
Insulin
- Stimulates hepatic glycogen synthesis
- Increase protein synthesis
- Facilitates triglyceride synthesis and storage by adipocytes
- Inhibits lipolysis
- Stimulates peripheral uptake of glucose
MOA of Insulin
- inject 10 -15 mins before mealtime
- typically used in conjunction with longer-acting insulin
RAPID acting
Inject at least 20-30 minutes before mealtime
SHORT acting
- commonly used twice daily
- often combined with rapid or short acting insulin
INTERMEDIATE acting
- covers insulin needs for 24 hrs
- if needed, often combined with rapid or short acting insulin
LONG acting
- combination of intermediate and short acting insulin
- commonly used twice daily before mealtime
PRE-MIXED
Long acting no peak
Lantus or Glargine
Amylin Receptor Agonists
Pramlintide
Enhance post-prandial control in individual with
T1DM and T2DM
Amylin Receptor Agonists indication
Gastric motility disorder
Amylin Receptor Agonists contraindication
- Slow gastric emptying time
- Decrease post-prandial glucagon secretion
- Suppresses appetite
MOA of Amylin Receptor Agonists
GLP-1 agonist
Incretin mimetics
Incretin mimetics
Exenatide, Liraglutide, -glutides
Management of T2DM
Indication of incretin mimetics
Severe GI motility, pancreatitis, renal or hepatic impairment
Contraindication of incretin mimetics
- Increase glucose-dependent insulin secretion,
- Decrease hepatic glucose output
- Increase beta cell growth and replication
- Slow gastric emptying time
- Enhance satiety or feeling of fullness to suppress appetite
MOA of Incretin mimetics
Dipeptidyl peptidase IV (DPP IV) inhibitors
Sitagliptin, Saxagliptin, Linagliptin
Patients with T2DM with normal or impaired
hepatic and renal function
Indication of Dipeptidyl peptidase IV (DPP IV) inhibitors
Pancreatitis
Contraindication of Dipeptidyl peptidase IV (DPP IV) inhibitors
- Prevents the inactivation of incretin hormones by the
enzyme DPP IV during hyperglycemia - Inhibits the breakdown of GLP-1 allowing increased
insulin secretion and decrease hepatic glucose production
MOA of Dipeptidyl peptidase IV (DPP IV) inhibitors
- Targets fasting blood glucose level
- Binds to and inhibits the ATP-sensitive potassium channels to increase the beta cell sensitivity to glucose and stimulate the secretion of insulin
- Protein-bound
- Prone to drug-drug interactions
Sulfonylureas
- Typically not prescribed since 2nd gen has fewer ADR
- Associated with thrombocytopenia, agranulocytosis, hemolytic anemia, hyponatremia, SIADH, disulfiram-like reactions
1st Generation Sulfonyureas
- Tolbutamide, Tolazamide, Chlorpropamide
1st Generation Sulfonyureas
Glyburide, Glipizide, Glimepiride
2nd Generation Sulfonyureas
Meglitinide
Repaglinide
Phenylalanine derivatives
Netaglinide
Insulin Secretagogues
Sulfonyureas, Meglitinide, Phenylalanine derivatives
- Management for T2DM
- Targets post-prandial glucose control
Indication of Meglitinide and Phenylalanine derivatives
Binds to ATP-sensitive potassium channel to stimulate secretion of insulin from pancreatic Beta cell, reduces hepatic glucose output
MOA of Meglitinide and Phenylalanine derivatives
Severe renal and hepatic dysfunction
- Used in caution in elderly due to increased risk of fall
Contraindication of Meglitinide and Phenylalanine derivatives
Biguanides
Metformin
- Used for the glycemic control for management of T1DMand T2DM
- Targets fasting blood glucose
Biguanides
First line medication for newly diagnosed diabetes
Metformin
Renal disease, Hepatic impairment, HF
Contraindication of Biguanides
- Inhibits hepatic glucose output, thus exerting beneficial effects on fasting blood glucose level
- Promotes glucose uptake by fat and muscles, improving insulin sensitivity
- Minor role in decreasing intestinal absorption of glucose
MOA of biguanides
Thiazolidinediones (TZDs)
Pioglitazone, Rosiglitazone
Glycemic control in T2DM and primarily affects
fasting blood glucose level
Indication of Thiazolidinediones (TZDs)
Hepatic dysfunction, Class III/IV HF, Anemia, Fracture risk
Contraindication of Thiazolidinediones (TZDs)
Alpha-glucosidase Inhibitors
Acarbose, Miglitol
Management of post-prandial blood glucose
Indication of Alpha-glucosidase Inhibitors
IBD
Contraindication of Alpha-glucosidase Inhibitors
with serum creatinine of > 2.0mg/dL or
creatinine clearance of < 25mL/min; hepatic impairment
Acarbose
Competitive inhibition of alpha-glucosidase in the
intestinal brush border, which leads to slower
absorption of complex carbohydrates
MOA of Alpha-glucosidase Inhibitors
Sodium-Glucose Cotransporter Inhibitors
-New class of oral hypoglycemic agent
Canagliflozin, Dapagliflozin, and Empagliflozin
Selectively and reversibly inhibits the sodium-glucose
cotransporter which is selectively expressed in the
proximal renal tubule
MOA of Sodium-Glucose Cotransporter Inhibitors
T2 DM + Atherosclerotic
Cardiovascular Disease (ASCVD)
Monotherapy of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) or Sodium Glucose Cotransporter 2 (SGL2) Inhibitors [Canagliflozin, Dapagliflozin, Empagliflozin]
T2 DM + Atherosclerotic
Cardiovascular Disease (ASCVD)
> If A1C above target
consider combination therapy or add Thiazolidinediones (TZDs) [Pioglitazone, Rosiglitazone]
T2 DM + Heart Failure
Sodium-Glucose Cotransporter 2 (SGL2) Inhibitors [Canagliflozin, Dapagliflozin, Empagliflozin]
T2 DM + Chronic Kidney Disease (CKD)
Sodium-Glucose Cotransporter 2 (SGL2) Inhibitors [Canagliflozin, Dapagliflozin, Empagliflozin] OR Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) [Exenatide,
Liraglutide]
T2 DM + Chronic Kidney Disease (CKD)
> If A1C above target
consider combination therapy of SGL2I and GLP-1 RA
Glycemic Control
Metformin
If glycemic control is not achieved
combination therapy with other oral hypoglycemic agents
(Efficacy for Glucose Lowering) Very high
- high dose dulaglutide
- semaglutide
- tirzepatide
- insulin
- combination GLP-1RA-Insulin
(Efficacy for Glucose Lowering) High
- GLP-1 RA
- Metformin
- SGLT2i
- Sulfonylureas
- TZDs
(Efficacy for Glucose Lowering) Intermediate
DPP4 Inhibitors
(Efficacy for Weight Loss) Very high
- Semaglutide
- Tirzepatide
(Efficacy for Weight Loss) High
- Dulaglutide
- Liraglutide
(Efficacy for Weight Loss) Intermediate
GLP-1RA, SGLT2i
(Efficacy for Weight Loss) Neutral
- DPP4 inhibitors
- Metformin
T2 DM + Weight Control Problems
- Set individualized weight management goals
- Lifestyle modification, nutrition programs,
physical activity, metabolic surgery
HbA1c <9%
FBS < 250
- Monotherapy
- Option for combination
HbA1c >= 9%
FBS >= 250
- combination
- insulin
World diabetes day
Nov 14
three things to remember in DM
chronic, uncontrolled, and hyperglycemia
Insulin should not be stopped (t or f)
T
Blood glucose less than 13 mmol/L (or less than 230 mg/dL)
Continue with current medication
Blood glucose 13-22 mmol/L (or 230-390 mg/dL)
Patient should inject insulin by 2 units per injection, even if unable to eat
Blood glucose greater than 22 mmol/L (or 390 mg/dL)
Patient should increase his insulin by 4 units per injection, even if unable to eat
