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Questions and Answers
What is the typical glucose level in a patient with HHS?
What is the typical glucose level in a patient with HHS?
In DKA, plasma ketones are indicated by a result of +++++.
In DKA, plasma ketones are indicated by a result of +++++.
True
What type of saline is recommended for fluid correction in DKA management?
What type of saline is recommended for fluid correction in DKA management?
1/2 NS
The sodium level in a patient with HHS typically ranges from ____ meq/L.
The sodium level in a patient with HHS typically ranges from ____ meq/L.
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Match the following parameters with their values in DKA:
Match the following parameters with their values in DKA:
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Which of the following conditions is NOT associated with Diabetes Mellitus?
Which of the following conditions is NOT associated with Diabetes Mellitus?
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Acromegaly is a genetic disease associated with Diabetes Mellitus.
Acromegaly is a genetic disease associated with Diabetes Mellitus.
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Name one genetic disease associated with Diabetes Mellitus.
Name one genetic disease associated with Diabetes Mellitus.
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___ is a condition characterized by an excessive production of growth hormone, leading to enlarged features.
___ is a condition characterized by an excessive production of growth hormone, leading to enlarged features.
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Match the following endocrine disorders with their brief descriptions:
Match the following endocrine disorders with their brief descriptions:
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Which of the following is NOT a cause of Type 3 Diabetes Mellitus?
Which of the following is NOT a cause of Type 3 Diabetes Mellitus?
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Macrovascular complications are common in Type 3a Diabetes Mellitus.
Macrovascular complications are common in Type 3a Diabetes Mellitus.
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What is the gold standard investigation for diagnosing pancreatic causes of diabetes?
What is the gold standard investigation for diagnosing pancreatic causes of diabetes?
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Type 3c diabetes is associated with __________ due to large ductal calculi.
Type 3c diabetes is associated with __________ due to large ductal calculi.
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Match the following drugs with their associated categories causing Diabetes Mellitus:
Match the following drugs with their associated categories causing Diabetes Mellitus:
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Which of the following is a feature of Hyperosmolar Hyperglycemic State (HHS)?
Which of the following is a feature of Hyperosmolar Hyperglycemic State (HHS)?
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In HHS, blood glucose levels must be monitored every four hours.
In HHS, blood glucose levels must be monitored every four hours.
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What is the initial stat dose of regular insulin administered intravenously in HHS treatment?
What is the initial stat dose of regular insulin administered intravenously in HHS treatment?
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In HHS, fluid replacement is typically around ______ liters.
In HHS, fluid replacement is typically around ______ liters.
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Match the following components of HHS treatment to their correct description:
Match the following components of HHS treatment to their correct description:
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What is a common symptom of ketoacidosis?
What is a common symptom of ketoacidosis?
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High anion gap metabolic acidosis is a characteristic finding in ketoacidosis.
High anion gap metabolic acidosis is a characteristic finding in ketoacidosis.
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What causes the fruity odor of the breath in patients with ketoacidosis?
What causes the fruity odor of the breath in patients with ketoacidosis?
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In ketoacidosis, excessive ________ hormones lead to lipolysis and ketone body formation.
In ketoacidosis, excessive ________ hormones lead to lipolysis and ketone body formation.
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Match the following signs/symptoms with their description:
Match the following signs/symptoms with their description:
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Which of the following tissues primarily uses GLUT-4 for insulin-dependent glucose uptake?
Which of the following tissues primarily uses GLUT-4 for insulin-dependent glucose uptake?
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Insulin is a polypeptide consisting of 51 amino acids.
Insulin is a polypeptide consisting of 51 amino acids.
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What is one consequence of decreased amino acid uptake due to insulin deficiency?
What is one consequence of decreased amino acid uptake due to insulin deficiency?
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Insulin acts via a __________ receptor.
Insulin acts via a __________ receptor.
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Match the following complications of diabetes mellitus with their descriptions:
Match the following complications of diabetes mellitus with their descriptions:
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Which of the following statements about GLP-1 is true?
Which of the following statements about GLP-1 is true?
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GLP-1 is associated with reducing body weight.
GLP-1 is associated with reducing body weight.
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Name one acute complication of insulin deficiency in diabetes mellitus.
Name one acute complication of insulin deficiency in diabetes mellitus.
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GLP-1 enhances _____ cell glucose responsiveness.
GLP-1 enhances _____ cell glucose responsiveness.
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Match the following GLP-1 characteristics with their descriptions:
Match the following GLP-1 characteristics with their descriptions:
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Which of the following medications is NOT associated with a risk of hypoglycemia?
Which of the following medications is NOT associated with a risk of hypoglycemia?
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Gliclazide has a neutral effect on weight.
Gliclazide has a neutral effect on weight.
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Name one type of ultra-short acting insulin.
Name one type of ultra-short acting insulin.
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SGLT-2 antagonists, such as ______ and ______, primarily function by blocking the NLRP3 inflammasome pathway.
SGLT-2 antagonists, such as ______ and ______, primarily function by blocking the NLRP3 inflammasome pathway.
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Match the following oral hypoglycemic drugs with their characteristics:
Match the following oral hypoglycemic drugs with their characteristics:
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What characterizes the dawn phenomenon?
What characterizes the dawn phenomenon?
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The Somogyi effect is caused by insufficient nighttime insulin doses.
The Somogyi effect is caused by insufficient nighttime insulin doses.
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What is the recommended nighttime insulin dose of Glargine?
What is the recommended nighttime insulin dose of Glargine?
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The components of Continuous Glucose Monitoring System (CGMS) include a Continuous Glucose Monitor, a cable, a glucose sensor, and a ______.
The components of Continuous Glucose Monitoring System (CGMS) include a Continuous Glucose Monitor, a cable, a glucose sensor, and a ______.
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Match the following terms with their descriptions:
Match the following terms with their descriptions:
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What is the primary function of GLUT4?
What is the primary function of GLUT4?
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GLUT2 is primarily found in the brain and is responsible for glucose uptake.
GLUT2 is primarily found in the brain and is responsible for glucose uptake.
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Which incretin hormone is known to augment insulin production in response to a glucose meal?
Which incretin hormone is known to augment insulin production in response to a glucose meal?
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SGLT2 is responsible for the __________ of glucose in the proximal convoluted tubule of the kidney.
SGLT2 is responsible for the __________ of glucose in the proximal convoluted tubule of the kidney.
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Which condition is associated with undetectable glucose levels and high C-peptide levels?
Which condition is associated with undetectable glucose levels and high C-peptide levels?
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Match the following GLUT transporters with their tissue locations:
Match the following GLUT transporters with their tissue locations:
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Liraglutide is an example of a recombinant GLP-1 used in diabetes treatment.
Liraglutide is an example of a recombinant GLP-1 used in diabetes treatment.
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What is the role of incretin hormones in glucose metabolism?
What is the role of incretin hormones in glucose metabolism?
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Study Notes
Endocrinopathies Associated with DM
- Cushing's syndrome, Acromegaly, Hyperthyroidism, Hyperparathyroidism, Pheochromocytoma, Glucoganoma, Somatostatinoma are conditions associated with Diabetes Mellitus
Genetic Diseases Associated with DM
- Down's syndrome, Klinefelter syndrome, Friedreich's ataxia, Huntington's, Prader Willi, Porphyria, Myotonic dystrophy, Wolfram syndrome, Laurence-Moon-Biedl syndrome are conditions associated with Diabetes Mellitus
DKA vs HHS Lab Values
- DKA: Glucose 350-400 mg/dL, Plasma Ketones ++, pH ↓
- HHS: Glucose >800 mg/dL, Plasma Ketones ++++++, pH (N)
- Both DKA & HHS: NaHCO3 (mEq/L) ↓
- Both DKA & HHS: Anion Gap (N)/↓
Type 3 DM (Pancreatic DM)
- Tropical chronic calcific pancreatitis (TCCP)
- Cystic fibrosis
Type 3a DM
- Alzheimer's disease
Type 3c: TCCP DM
- Large ductal calculi + duct dilatation + marked fibrosis
- Increased risk of pancreatic cancer
- Lean, young ketosis -ve DM
- 2nd-3rd decade, Younger males
- Diabetes Mellitus (DM)
- Steatorrhea
- Abdominal pain
- Nephropathy
- Macrovascular complications are rare
- ERCP (Gold standard)
Type 3d: Drugs Causing DM
- Immunosuppressants: Tacrolimus
- Anticancer: L-asparginase
- Endocrine: Growth Hormone (GH)
- ANS: Beta-agonist
- Psychiatric: Olanzapine
- Diuretics: Thiazide
- Act independent of insulin: Nicotinic acid, statins, aspirin
Other Conditions Associating with DM
- Hemochromatosis
- IgG4 related disease
Hyperosmolar Hyperglycemic State (HHS) Pathophysiology & Features
- Relative insulin deficiency + mild increase in counter-regulatory hormones
- T2DM > TIDM
- Elderly patient
- Precipitating factor(+) e.g., LRTI
- Develops over a week's time
HHS Treatment
- 2 IV lines inserted
- Fluids: Replace 6-9 L of fluid
- Regular insulin: Stat dose 0.1 u/kg/kg IV
- Infusion 0.1 u/kg/hr
- Monitor blood glucose every hour
- When values are 200 mg/dL, switch fluids from NS to 5% dextrose
HHS Prognosis
- Good
Insulin Physiology
- Islets of Langerhans (2% of pancreatic volume)
- Polypeptide (51 amino acids) made of a chain, connected by disulfide bonds
- Acts via Tyrosine kinase (TK) receptor
Carbohydrate Metabolism
- Insulin-dependent glucose uptake via GLUT-4: Skeletal muscle, Adipose tissue, Heart
- Regulates glucose production: (-) gluconeogenesis, (-) glycogenolysis
Protein Metabolism
- ↓ amino acid uptake → Weakness
- ↓ amino acid synthesis
- ↑ proteolysis → Wasting
Fat Metabolism
- Lipolysis
Specific complications of diabetes mellitus (DM)
- Mucormycosis
- Emphysematous cholecystitis
- Emphysematous pyelonephritis
- Malignant otitis externa
Absolute insulin deficiency (TIDM >> T2DM)
- Excessive counter-regulatory hormones (Glucagon/Epinephrine/Cortisol)
- ↑ CPT I (Carnitine Palmitoyl Transferase)
- Free fatty acids undergo β-oxidation in mitochondria
- Lipolysis
- ↑ Acetyl-CoA formation
- Ketone body formation
- Ketosis/Ketoacidosis
Clinical Features of DKA
- Nausea/vomiting
- Thirst/Polyuria
- Respiratory distress out of proportion to lung signs
- Dehydration
- Tachycardia
Investigations for DKA
- ABG: High anion gap metabolic acidosis (HAGMA)
- β-Hydroxybutyrate level
- Urine Ketones
- CBC
- RFT
- S.Electrolytes
Other Findings
- Abdominal Pain
- Shortness of breath
- Acidotic breath (fruity odor)
- Abdominal tenderness (D/D: Acute pancreatitis)
GLP-1 vs GIP
- GLP-1: Source- L cells/ileum & colon, Glucose dependent insulin release +++, Enhances Beta cell glucose responsiveness +++, Suppresses glucagon release +++, Stimulates beta cell expansion +++, Inhibition of gastric emptying +++, Enhances satiety +++, Reduces body weight +++, Half life 1-2 min (Rapidly degraded by DPP-4)
- GIP: Source- K cells/jejunum, Glucose dependent insulin release +++, Enhances Beta cell glucose responsiveness +++, Enhances satiety +++, Reduces body weight +++, Half life 5-7 min
Advantages of recombinant GLP-1 over other hypoglycemic agents
- Promotes weight loss (used in Rx of NASH/NAFLD)
- No risk of hypoglycemia
- Cardio-protective
- ↑ HbA1c reduction potential
- Nephroprotective
Complications of Insulin deficiency (DM)
- Acute: Diabetic ketoacidosis (DKA), Hyperglycemic hyperosmolar state (HHS)
- Chronic: Retinopathy, Nephropathy, Peripheral neuropathy
- Macrovascular: Atherosclerotic CVD, CKD
Precipitating factors of Diabetic KetoAcidosis (DKA)
- Infection
- Infarction
- Pregnancy
- Cocaine
- Non-compliance to Rx
Oral Hypoglycemic Drugs
- Biguanide: Metformin: Weight loss (mild), HbA1c reduction good (1-2%), No hypoglycemia risk, No cardiac risk, Renal: C/1: GFR < 30 ml/min, Combats resistance, Acts by ↑ AMP Kinase, No effect on comorbidity, macrovascular disease
- Sulfonylurea: Gliclazide: Only drug in use, Vasodilator (NO), Antioxidant, Other drugs are not in use due to cardiotoxicity, Weight gain, HbA1c reduction good (1-2%), Risk: Hypoglycemia
- Oral GLP-1 Analogue: Semaglutide: New, Liraglutide, Tirzepatide, Used in NASH, HbA1c reduction (2-2.5%), Protective glycemic, Cardioprotective, Renoprotective, Tirzepatide: Newer drug, Dual GLP-1, GIP action, Weight loss (max)
- SGLT-2 Antagonist: Dapagliflozin: Empagliflozin, HbA1c reduction: 1.5-2%, Blocks: NLRP3 inflammasome pathway, Blocks atherosclerosis, Reduces other comorbidities,
- Gliptins: Linagliptin: Weight neutral
Indications of Insulin therapy
- Hybrid diabetes form
- T1DM
- GDM
- HbA1c ≥ 9.5%
- macro/micro vascular involvement
- Ketosis
- Significant Polyurea, polydipsia and weight loss
Types of Insulin
- Ultra Short: Lispro, Aspart
- Short: Regular
- Intermediate: NPH
- Long: Glargine, Detemir
- Ultralong: Degludec
CBGM (Continuous blood glucose monitoring)
- CBGM should be done before starting insulin therapy
Dawn Phenomenon vs Somogyi Effect
- Dawn Phenomenon: Characterized by early-morning hyperglycemia.
- Somogyi Effect: Characterized by excess in nighttime insulin doses, leading to early-morning hyperglycemia and midnight hypoglycemia.
Continous Glucose Monitoring System (CGMS) Components
- Continuous Glucose Monitor (CGM)
- Cable
- Glucose Sensor
- Com-station/Charger
Insulin Regime
- Regular Insulin: 8 units - 8 units - 8 units
- Long-Acting Insulin: Glargine: 16 units (Nightly) or Degludec: 16 units (Alternate Nights) or Regular Insulin: 16 units (Twice daily)
Insulin Administration Instructions
- Frequency: Perform blood glucose checks before and after breakfast, lunch, and dinner 6 times
- Dose Adjustment: Insulin doses can be adjusted by increasing or decreasing by 4 unit(s) based on measured blood sugar level(s)
Glucose Transporter (GLUTs)
- GLUT1: Brain, kidney, colon, placenta, erythrocyte - Uptake of glucose
- GLUT2: Liver, pancreatic β cell, small intestine, kidney - Rapid uptake and release of glucose
- GLUT3: Brain, kidney, placenta - Uptake of glucose
- GLUT4: Heart and skeletal muscle, adipose tissue - Insulin-stimulated uptake of glucose
- GLUT5: Small intestine - Uptake of fructose
SGLT1 & SGLT2
- SGLT1: Small intestine - Active uptake of glucose from lumen of intestine
- SGLT2: Kidney - Reabsorption of glucose in proximal convoluted tubule of kidney
Conditions associated with Glucose & C-peptide level:
- Undetectable Glucose | ↑ C-peptide: TIDM
- ↑ Glucose | ↑ C-peptide: T2DM
- ↓ Glucose | ↓ C-peptide: Insulinoma
- ↓ Glucose | ↓ C-peptide: Exogenous insulin
Incretin Hormones
- Incretins: GLP-1, GIP
- Mechanism: Augment insulin production in response to a glucose meal (intrajejunal glucose).
Applied Aspects of Incretins
- Recombinant GLP-1 used in the Rx of DM.Not easily degraded by dipeptidyl peptidase-4 (DPP-4)
- Exenatide (Pancreatitis risk)
- Liraglutide s/c
- Semaglutide oral (↑ weight loss)
- Dual GLP-1/GIP analogues (new): Tirzepatide
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Description
Explore the intricate relationship between diabetes mellitus (DM) and various endocrinopathies and genetic diseases. This quiz covers conditions like Cushing's syndrome and Down's syndrome, as well as compares lab values between DKA and HHS. Test your knowledge on the types of diabetes related to both endocrine and genetic factors.
