DIABETES MELLITUS part 2

Question 1

What is the underlying cause of type 1 diabetes?

Answer 1

The underlying cause of type 1 diabetes is unclear, but there may be a genetic component. Certain viruses, such as Coxsackie B and enterovirus, may trigger it.

Question 2

What are the classic symptoms of hyperglycemia in type 1 diabetes?

Answer 2

The classic triad of symptoms of hyperglycemia in type 1 diabetes includes polyuria (excessive urine), polydipsia (excessive thirst), and weight loss (mainly through dehydration).

Question 3

What is the role of insulin in glucose metabolism?

Answer 3

Insulin, produced by beta cellsin the Islets of Langerhans in the pancreas, is an anabolic hormone. It reduces blood sugar levels by causing cells in the body to absorb glucose from the blood and use it as fuel. It also prompts muscle and liver cells to absorb glucose from the blood and store it as glycogen in a process called glycogenesis. Without insulin, cells cannot take up and use glucose, leading to hyperglycemia.

Question 4

What is glucagon, and what is its role in glucose metabolism?

Answer 4

Glucagon, produced by alpha cells in the Islets of Langerhans in the pancreas, is a catabolic hormone. It is released in response to low blood sugar levels and stress, working to increase blood sugar levels. Glucagon instructs the liver to break down stored glycogen and release it into the blood as glucose in a process called glycogenolysis. It also signals the liver to convert proteins and fats into glucose through gluconeogenesis.

Question 5

When does ketogenesis occur, and what are ketones?

Answer 5

Ketogenesis, the production of ketones, occurs when there is insufficient glucose supply and glycogen stores are exhausted, as in prolonged fasting. Ketones are water-soluble fatty acids produced by the liver from fatty acids. They can be used as fuel, cross the blood-brain barrier to be used by the** brain**, and are normal and not harmful under fasting conditions or on very low carbohydrate, high-fat diets. Ketone levels can be measured in the urine with a dipstick test and in the blood using a ketone meter.

Question 6

What is diabetic ketoacidosis (DKA), and when does it occur?

Answer 6

Diabetic ketoacidosis (DKA) occurs as a consequence of inadequate insulin. It can occur in the initial presentation of type 1 diabetes, when an existing type 1 diabetic is unwell for another reason, often with an infection, or when an existing type 1 diabetic is not adhering to their insulin regime. The three key features of DKA are ketoacidosis, dehydration, and potassium imbalance.

Question 7

What is the pathophysiology of diabetic ketoacidosis (DKA)?

Answer 7

Diabetic ketoacidosis (DKA) occurs due to inadequate insulin. The lack of insulin leads to hyperglycemia, ketogenesis (production of ketones), and metabolic acidosis. DKA can be triggered by various scenarios in type 1 diabetes, resulting in life-threatening metabolic acidosis. The three key features of DKA are ketoacidosis, dehydration, and potassium imbalance.

Question 8

What are the three key features of diabetic ketoacidosis (DKA)?

Answer 8

The three key features of diabetic ketoacidosis (DKA) are ketoacidosis, dehydration, and potassium imbalance.

Question 9

What is the role of the kidneys in buffering ketones?

Answer 9

The kidneys buffer ketone acids (ketones) in healthy individuals, preventing the blood from becoming acidotic.

Question 10

What is hyperglycaemic hyperosmolar syndrome (HHS)?

Answer 10

Hyperglycaemic hyperosmolar syndrome (HHS) is a severe hyperglycemia without significant ketosis, characteristic of type 2 diabetes.

Question 11

How does the pathophysiology of HHS differ from DKA?

Answer 11

The pathophysiology of HHS is similar to DKA, but in HHS, there are still small amounts of insulin being secreted, preventing ketosis. However, the insulin level is not high enough to lower blood glucose to a safe level.

Question 12

What are the clinical features of hyperglycaemic hyperosmolar syndrome?

Answer 12

Clinical features of HHS include dehydration due to polyuria, polydipsia, nausea, vomiting, and stupor/coma. The degree of impaired consciousness is directly related to the level of osmolarity.

Question 13

What are the key investigations used to diagnose hyperglycaemic hyperosmolar syndrome?

Answer 13

HHS is characterized by profound hyperglycemia (glucose > 33.3 mmol/L), hyperosmolality (serum osmolarity > 320 mmol/kg, measured directly or calculated as 2 x Na+ + glucose +

Question 14

What is the cause of ketoacidosis in the absence of insulin?

Answer 14

In the absence of insulin, the body’s cells cannot recognize glucose, leading to the liver producing ketones as an alternative fuel source. Over time, elevated levels of glucose and ketones result. Initially, the kidneys produce bicarbonate to counteract ketone acids and maintain a normal pH. However, prolonged ketone acid presence depletes bicarbonate, leading to ketoacidosis.

Question 15

How does dehydration occur in the context of hyperglycemia?

Answer 15

High blood glucose levels overwhelm the kidneys, causing glucose to leak into the urine. The osmotic diuresis, a process where glucose in the urine draws water out, leads to increased urine production (polyuria) and severe dehydration. Dehydration contributes to excessive thirst (polydipsia).

Question 16

What role does insulin play in potassium balance?

Answer 16

Insulin normally drives potassium into cells. Without insulin, potassium is not added to and stored in cells. While serum potassium levels can be high or normal due to kidney balancing, total body potassium is low because no potassium is stored in the cells. Treatment with insulin can rapidly lead to severe hypokalemia (low serum potassium), posing a risk of fatal arrhythmias.

Question 17

What are the key features of the presentation of diabetic ketoacidosis?

Answer 17

The presentation of diabetic ketoacidosis includes hyperglycemia, dehydration, ketosis, metabolic acidosis (with low bicarbonate), and potassium imbalance. Patients may experience symptoms such as polyuria, polydipsia, nausea and vomiting, acetone smell in the breath, weight loss, hypotension (low blood pressure), and altered consciousness.

Question 18

What may trigger diabetic ketoacidosis, and why is it essential to investigate?

Answer 18

Diabetic ketoacidosis may be triggered by an underlying condition, such as an infection. It is crucial to investigate and look for signs of infections and other underlying pathology in any patient with DKA, as treating the underlying cause is essential for comprehensive management.

Question 19

What are the diagnostic criteria for diabetic ketoacidosis (DKA)?

Answer 19

The diagnosis of DKA requires all three of the following criteria: hyperglycemia (e.g., blood glucose above 11 mmol/L), ketosis (e.g., blood ketones above 3 mmol/L), and acidosis (e.g., pH below 7.3).

Question 20

What are the priorities in the treatment of diabetic ketoacidosis (DKA)?

Answer 20

The priorities in the treatment of DKA are fluid resuscitation to correct dehydration, electrolyte disturbance, and acidosis. The primary goal is to address dehydration, potassium imbalance, and acidosis, as these are life-threatening aspects of DKA.

Question 21

What is the “FIG-PICK” mnemonic, and how does it aid in managing DKA?

Answer 21

The “FIG-PICK” mnemonic summarizes the principles of managing DKA: Fluids (IV fluid resuscitation with normal saline), Insulin (fixed-rate insulin infusion), Glucose (monitoring and adding glucose infusion when blood glucose is less than 14 mmol/L), Potassium (adding potassium to IV fluids and monitoring closely),** Infection (treating underlying triggers like infection)**, Chart fluid balance, and Ketones (monitoring blood ketones, pH, and bicarbonate). This aids in a systematic approach to DKA management.

Question 22

What are the key complications during the treatment of DKA?

Answer 22

The key complications during the treatment of DKA include hypoglycemia (low blood sugar), hypokalemia (low potassium), cerebral edema (particularly in children), and pulmonary edema secondary to fluid overload or acute respiratory distress syndrome.

Question 23

What considerations should be taken into account regarding potassium infusion in DKA treatment?

Answer 23

Under normal circumstances, the rate of potassium infusion should not exceed 10 mmol/hour to avoid inducing arrhythmia or cardiac arrest. However, in DKA, rates up to 20 mmol/hour may be used. Higher rates are only employed in specific scenarios under expert supervision with cardiac monitoring and through a central line rather than a peripheral cannula. Monitoring for potassium levels and ECG is crucial during the infusion.

Question 24

Why are autoantibodies and serum C-peptide checked in some cases?

Answer 24

Autoantibodies and serum C-peptide are checked in cases where there is doubt about whether a patient has type 1 or type 2 diabetes. Autoantibodies associated with type 1 diabetes include anti-islet cell antibodies, anti-GAD antibodies, and anti-insulin antibodies. Serum C-peptide, a measure of insulin production, is helpful in distinguishing between low and high insulin production.

Question 25

What are the components of long-term management for type 1 diabetes?

Answer 25

Long-term management of type 1 diabetes involves subcutaneous insulin, monitoring dietary carbohydrate intake, monitoring blood sugar levels upon waking, at each meal, and before bed, and monitoring and managing complications, both short and long term. Patient education is crucial for understanding and engaging with the condition, as type 1 diabetes is a lifelong condition that requires active patient involvement.

Question 26

What is a basal-bolus regime in the context of insulin therapy for type 1 diabetes?

Answer 26

A basal-bolus regime involves a combination of **background, long-acting insulin injected once a day and short-acting insulin injected 30 minutes before consuming carbohydrates (e.g., at meals)**. This regimen helps mimic the body's natural insulin production pattern and provides better control over blood sugar levels throughout the day. Patients are advised to cycle their injection sites to avoid **lipodystrophy**, a condition where subcutaneous fat hardens and affects insulin absorption.

Question 27

What are insulin pumps, and what are their advantages and disadvantages?

Answer 27

Insulin pumps are small devices that continuously infuse insulin at different rates to control blood sugar levels. They offer better blood sugar control, more flexibility with eating, and fewer injections. However, disadvantages include difficulties learning to use the pump, the need for constant attachment, potential blockages in the infusion set, and a small risk of infection. Tethered pumps have visible tubes connected to the pump, while patch pumps sit directly on the skin without visible tubes. Both types aim to provide convenient insulin delivery.

Question 28

What is the purpose of a pancreas transplant, and when is it considered?

Answer 28

A pancreas transplant involves implanting a donor pancreas to produce insulin. It is considered in patients with severe hypoglycaemic episodes and those also requiring kidney transplants. The original pancreas is left in place for digestive enzyme production. The procedure is reserved for specific cases due to significant risks and the need for life-long immunosuppression to prevent rejection.

Question 29

What is islet transplantation, and what role do islet cells play?

Answer 29

Islet transplantation involves inserting donor islet cells into the patient's liver. Islet cells produce insulin and assist in managing diabetes. However, patients often still require insulin therapy after islet transplantation. This procedure is an alternative to pancreas transplantation and may be considered in specific cases.

Question 30

What is the purpose of monitoring HbA1c levels in diabetes management?

Answer 30

HbA1c measures glycated hemoglobin, reflecting the average glucose level over the previous 2-3 months. It provides a long-term indicator of blood sugar control. Monitored every 3 to 6 months, HbA1c is a lab test that helps track average sugar levels, guiding diabetes management decisions.

Question 31

How does a flash glucose monitor, such as FreeStyle Libre, work?

Answer 31

Flash glucose monitors, like FreeStyle Libre, use a sensor on the skin to measure glucose levels in the interstitial fluid. The sensor records readings at short intervals, providing an overview of glucose levels over time. Users swipe their mobile phones over the sensor to collect readings. These monitors offer convenience but have a 5-minute lag compared to blood glucose. Sensors need replacement every 2 weeks. If hypoglycemia is suspected, capillary blood glucose testing is necessary due to the delay.

Question 32

What is the difference between continuous glucose monitors (CGM) and flash glucose monitors?

Answer 32

Continuous glucose monitors (CGM) and flash glucose monitors both use a sensor on the skin to monitor sugar levels in interstitial fluid. However, CGMs send readings over Bluetooth and do not require patients to scan the sensor manually. The key distinction lies in the automated transmission of readings, enhancing user convenience compared to flash glucose monitors.

Question 33

What is a closed-loop system or artificial pancreas in diabetes management?

Answer 33

A closed-loop system, also known as an artificial pancreas, combines a continuous glucose monitor and an insulin pump. These devices communicate to automatically adjust insulin based on glucose readings. While the system aids in blood sugar control, patients need to input carbohydrate intake and adjust for activities like strenuous exercise. The closed-loop system represents an advanced approach to diabetes management.

Question 34

What are short-term complications in diabetes management?

Answer 34

Short-term complications in diabetes management involve immediate issues with insulin and blood glucose. These include hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar), which may lead to diabetic ketoacidosis (DKA). Hypoglycemia symptoms include hunger, tremor, sweating, irritability, and more. Severe hypoglycemia can result in reduced consciousness, coma, and death if untreated. Hyperglycemia, without DKA, may require adjustments to insulin doses, and DKA cases necessitate inpatient management.

Question 35

What are long-term complications associated with chronic high blood glucose levels?

Answer 35

Chronic high blood glucose levels lead to long-term complications, including damage to endothelial cells of blood vessels. **Macrovascular** complications involve coronary artery disease, peripheral ischemia, stroke, and hypertension. **Microvascular** complications include peripheral neuropathy, retinopathy, and kidney disease (glomerulosclerosis). Additionally, chronic **high glucose levels impair the immune system**, increasing susceptibility to infections such as urinary tract infections, pneumonia, skin and soft tissue infections, and fungal infections like candidiasis. Monitoring and managing blood glucose levels are crucial to mitigate these complications.

Question 36

What are the common chronic complications related to diabetes?

Answer 36

Common chronic complications related to diabetes include macrovascular complications such as coronary artery disease, peripheral ischemia, stroke, and hypertension. Microvascular complications involve peripheral neuropathy, retinopathy, and kidney disease (glomerulosclerosis). Infection-related complications encompass urinary tract infections, pneumonia, skin and soft tissue infections, and fungal infections, particularly oral and vaginal candidiasis. Chronic complications arise due to damage caused by prolonged high blood glucose levels. Monitoring and managing blood glucose are essential to prevent or mitigate these complications.

Question 37

What is the simplified pathophysiology of Type 2 diabetes?

Answer 37

Repeated exposure to glucose and insulin leads to insulin resistance, requiring increased insulin production. Over time, the pancreas becomes fatigued and damaged, reducing insulin output. This, combined with a high carbohydrate diet, results in chronic high blood glucose levels (hyperglycaemia), leading to microvascular, macrovascular, and infectious complications similar to those in type 1 diabetes.

Question 38

What are the risk factors for Type 2 diabetes?

Answer 38

Non-modifiable risk factors include older age, ethnicity (Black African or Caribbean, South Asian), and family history. Modifiable risk factors include obesity, a sedentary lifestyle, and a high carbohydrate (particularly sugar) diet.

Question 39

What are the presenting features of diabetes?

Answer 39

Presenting features include tiredness, polyuria (frequent urination), polydipsia (excessive thirst), unintentional weight loss, opportunistic infections (e.g., oral thrush), slow wound healing, and glucose in urine (on a dipstick). Acanthosis nigricans, characterized by thickening and darkening of the skin, is often associated with insulin resistance.

Question 40

What is pre-diabetes, and how is it indicated?

Answer 40

Pre-diabetes indicates that a patient is heading towards diabetes without fitting the full diagnostic criteria. An HbA1c of 42–47 mmol/mol suggests pre-diabetes. HbA1c measures average glucose levels over the previous 2-3 months.

Question 41

How is type 2 diabetes diagnosed?

Answer 41

An HbA1c of 48 mmol/mol or above indicates type 2 diabetes. The sample is typically repeated after 1 month to confirm the diagnosis, unless there are symptoms or signs of complications. HbA1c is a blood test reflecting average glucose levels.

Question 42

What are the NICE guidelines for managing type 2 diabetes?

Answer 42

NICE guidelines (updated 2022) recommend a structured education program, a low-glycaemic-index, high-fiber diet, exercise, weight loss (if overweight), antidiabetic drugs, and monitoring and managing complications for managing type 2 diabetes.

Question 43

What are the treatment targets for HbA1c in type 2 diabetes?

Answer 43

The NICE guidelines recommend an HbA1c treatment target of 48 mmol/mol for new type 2 diabetics and 53 mmol/mol for patients requiring more than one antidiabetic medication. HbA1c is measured every 3 to 6 months until under control and stable.

Question 44

What is the first-line medical management for type 2 diabetes?

Answer 44

The first-line is metformin, which increases insulin sensitivity and decreases glucose production by the liver. Metformin, a biguanide, does not cause weight gain or hypoglycemia. Notable side effects include gastrointestinal symptoms (pain, nausea, diarrhea) and lactic acidosis (e.g., secondary to acute kidney injury). Modified-release metformin can be considered for patients with gastrointestinal side effects with standard-release metformin.

Question 45

What are second-line and third-line options for type 2 diabetes?

Answer 45

Second-line involves adding an SGLT-2 inhibitor (e.g., dapagliflozin) for patients with existing cardiovascular disease or heart failure. Second-line options also include a sulfonylurea, pioglitazone, DPP-4 inhibitor, or another SGLT-2 inhibitor. Third-line options include triple therapy with metformin and two second-line drugs or insulin therapy initiated by specialist diabetic nurses. In cases of triple therapy failure and BMI above 35 kg/m², switching one drug to a GLP-1 mimetic (e.g., liraglutide) is an option.

Question 46

Why are SGLT-2 inhibitors increasingly recommended in type 2 diabetes?

Answer 46

SGLT-2 inhibitors are recommended due to their cardiovascular benefits, especially in older patients with a QRISK score above 10%. NICE suggests considering SGLT-2 inhibitors alongside metformin as part of the first-line treatment in type 2 diabetics at high risk of cardiovascular disease. SGLT-2 inhibitors are recommended second-line as part of dual therapy in these patients. Diabetic ketoacidosis is a potential side effect to be aware of.

Question 47

What is the mechanism of action of SGLT-2 inhibitors?

Answer 47

SGLT-2 inhibitors block the sodium-glucose co-transporter 2 protein in the kidneys, preventing the reabsorption of glucose from urine back into the blood. This leads to increased glucose excretion in the urine, resulting in lower HbA1c, reduced blood pressure, weight loss, and improved heart failure. They may cause hypoglycemia when used with insulin or sulfonylureas. SGLT-2 inhibitors reduce the risk of cardiovascular disease and are licensed for heart failure and chronic kidney disease in some cases.

Question 48

What are the notable side effects of SGLT-2 inhibitors?

Answer 48

Notable side effects include glycosuria (glucose in the urine), increased urine output and frequency, genital and urinary tract infections (e.g., thrush), weight loss, diabetic ketoacidosis (especially with moderately raised glucose), and a potential increased risk of lower-limb amputation (more common with canagliflozin, unclear if it applies to others). Fournier's gangrene, a rare but severe infection of the genitals or perineum, is also mentioned. Patients starting SGLT-2 inhibitors should be informed about DKA features and when to seek emergency medical input.

Question 49

What is the mechanism of action of pioglitazone?

Answer 49

Pioglitazone is a thiazolidinedione that increases insulin sensitivity and decreases liver production of glucose. It does not typically cause hypoglycemia. Notable side effects include weight gain, heart failure, an increased risk of bone fractures, and a small increase in the risk of bladder cancer.

Question 50

What is the mechanism of action of sulfonylureas?

Answer 50

Sulfonylureas, with gliclazide being a common example, stimulate insulin release from the pancreas.

Question 51

What are the notable side effects of sulfonylureas?

Answer 51

Notable side effects of sulfonylureas include weight gain and hypoglycemia.

Question 52

What is the role of incretins in blood sugar regulation?

Answer 52

Incretins are hormones produced by the gastrointestinal tract in response to large meals. They reduce blood sugar by increasing insulin secretion, inhibiting glucagon production, and slowing absorption by the gastrointestinal tract. The main incretin is glucagon-like peptide-1 (GLP-1). Dipeptidyl peptidase-4 (DPP-4) inhibitors block the action of DPP-4, allowing increased incretin activity. GLP-1 mimetics imitate the action of GLP-1, resulting in reduced appetite, weight loss, and improved blood sugar control.

Question 53

What are DPP-4 inhibitors, and how do they work?

Answer 53

DPP-4 inhibitors, such as sitagliptin and alogliptin, block the action of dipeptidyl peptidase-4 (DPP-4), an enzyme that inhibits incretins. By inhibiting DPP-4, these drugs increase incretin activity, leading to increased insulin secretion, reduced glucagon production, and slowed absorption by the gastrointestinal tract. Notable side effects include headaches and a low risk of acute pancreatitis.

Question 54

How do GLP-1 mimetics work, and what are their notable side effects?

Answer 54

GLP-1 mimetics, like exenatide and liraglutide, imitate the action of glucagon-like peptide-1 (GLP-1). They are administered as subcutaneous injections. GLP-1 mimetics lead to reduced appetite, weight loss, and improved blood sugar control. Notable side effects include gastrointestinal symptoms such as discomfort, nausea, and diarrhea. Liraglutide is also used for weight loss in non-diabetic obese patients.

Question 55

What are the different types of insulin and their characteristics?

Answer 55

There are rapid-acting (e.g., NovoRapid), short-acting (e.g., Actrapid), intermediate-acting (e.g., Humulin I), and long-acting (e.g., Levemir, Lantus) insulins. Combinations of rapid-acting and intermediate-acting insulins are available, such as Humalog 25 (25:75), Humalog 50 (50:50), and Novomix 30 (30:70). These insulins have varying onset times and durations, and they are used to manage blood sugar levels in individuals with diabetes.

Question 56

What are the key complications of type 2 diabetes?

Answer 56

Key complications of type 2 diabetes include infections (e.g., periodontitis, thrush, and infected ulcers), diabetic retinopathy, peripheral neuropathy, autonomic neuropathy, chronic kidney disease, diabetic foot, gastroparesis (slow emptying of the stomach), and hyperosmolar hyperglycemic state. The management may involve medications like ACE inhibitors for hypertension and SGLT-2 inhibitors for chronic kidney disease. Additional treatments may be used for specific complications, such as phosphodiesterase-5 inhibitors for erectile dysfunction and prokinetic drugs for gastroparesis. Options for neuropathic pain include amitriptyline, duloxetine, gabapentin, and pregabalin.

Question 57

What is Hyperosmolar Hyperglycemic State (HHS)?

Answer 57

HHS is a rare but potentially fatal complication of type 2 diabetes characterized by hyperosmolality, hyperglycemia, and the absence of ketones.

Question 58

How does HHS differ from ketoacidosis?

Answer 58

HHS is distinguished from ketoacidosis by the absence of ketones in the blood.

Question 59

What are the key clinical features of HHS?

Answer 59

The key clinical features include polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension, and confusion.

Question 60

Why is HHS considered a medical emergency?

Answer 60

HHS has high mortality, making it a medical emergency that requires prompt and aggressive intervention. Involving experienced seniors early in the management is crucial.

Question 61

What is the primary treatment for HHS?

Answer 61

The primary treatment for HHS involves intravenous fluids to correct dehydration and restore normal blood volume. Careful monitoring of electrolytes and insulin therapy may also be part of the management.

Question 62

What distinguishes HHS from diabetic ketoacidosis?

Answer 62

The absence of ketones in HHS distinguishes it from diabetic ketoacidosis, where ketones are elevated.

Question 63

What are the potential triggers for HHS?

Answer 63

HHS is often triggered by infections or other stressors in individuals with type 2 diabetes.

Question 64

What are the neurological symptoms of HHS?

Answer 64

Neurological symptoms of HHS include confusion and altered mental status.

Question 65

How can HHS be prevented?

Answer 65

Preventive measures include proper management of diabetes, regular monitoring of blood glucose levels, and addressing potential triggers or stressors promptly.

Question 66

Why is involvement of experienced seniors crucial?

Answer 66

Due to the severity and complexity of HHS, the involvement of experienced senior clinicians early in the management is crucial for effective and appropriate intervention.

Question 67

What is the role of careful monitoring in HHS?

Answer 67

Careful monitoring is essential in HHS to track response to treatment, assess electrolyte balance, and manage any complications promptly.

Question 68

What is Diabetic Ketoacidosis (DKA)?

Answer 68

DKA is a life-threatening medical emergency commonly seen in children with a new diagnosis of type 1 diabetes. It involves extreme hyperglycaemic ketosis, metabolic acidosis, dehydration, and potassium imbalance.

Question 69

When does ketogenesis normally occur?

Answer 69

Ketogenesis normally occurs during prolonged fasting or very low carbohydrate diets when there is an insufficient supply of glucose, and glycogen stores are exhausted.

Question 70

What are ketones, and how are they measured?

Answer 70

Ketones are water-soluble fatty acids produced by the liver during ketogenesis. They can be measured in the urine using a urine dipstick and in the blood using a ketone meter. People in ketosis often have a characteristic acetone smell to their breath.

Question 71

What distinguishes diabetic ketoacidosis from ketosis?

Answer 71

Diabetic ketoacidosis (DKA) is characterized by extreme hyperglycaemic ketosis, leading to metabolic acidosis, while ketosis itself is a normal and not harmful process under fasting conditions or on a very low carbohydrate, high-fat diet.

Question 72

What is the pathophysiology of DKA in type 1 diabetes?

Answer 72

DKA occurs in type 1 diabetes when there is inadequate insulin production or injection. The main problems are ketoacidosis, dehydration, and potassium imbalance.

Question 73

Explain the process of ketoacidosis in DKA.

Answer 73

When cells lack fuel and initiate ketogenesis, glucose and ketone levels rise. Initially, bicarbonate buffers ketone acids, maintaining normal pH. As ketone acids deplete bicarbonate, the blood becomes acidic, leading to ketoacidosis.

Question 74

How does hyperglycaemia contribute to dehydration in DKA?

Answer 74

Hyperglycaemia overwhelms the kidneys, causing glucose to be filtered into the urine through osmotic diuresis. This leads to polyuria and severe dehydration.

Question 75

Describe the potassium imbalance in DKA.

Answer 75

Insulin normally drives potassium into cells. Without insulin, serum potassium can be high or normal, but total body potassium is low as it is not stored in cells. Treatment with insulin can rapidly lead to severe hypokalaemia and fatal arrhythmias.

Question 76

What are the most dangerous aspects of DKA?

Answer 76

The most dangerous aspects of DKA are dehydration, potassium imbalance, and acidosis, which can lead to fatal complications. The priority in treatment is fluid resuscitation followed by insulin infusion.

Question 77

Why is DKA considered a medical emergency?

Answer 77

DKA has life-threatening complications such as extreme hyperglycaemic ketosis, metabolic acidosis, and severe dehydration. Prompt and aggressive intervention is essential to prevent fatal outcomes.

Question 78

What is cerebral oedema, and why are children with DKA at risk?

Answer 78

Cerebral oedema is swelling of the brain due to the rapid shift of water from the extracellular to the intracellular space. Children with DKA are at risk due to dehydration and high blood sugar, and its management includes slowing IV fluids, mannitol, and hypertonic saline.

Question 79

Why should neurological observations be closely monitored in DKA?

Answer 79

Neurological observations, such as the Glasgow Coma Scale (GCS), should be monitored closely in DKA to detect signs of cerebral oedema, such as headaches, altered behaviour, bradycardia, or changes in consciousness.

Question 80

What are the symptoms of DKA?

Answer 80

Symptoms of DKA include polyuria, polydipsia, nausea, vomiting, weight loss, acetone smell in the breath, dehydration, hypotension, altered consciousness, and symptoms related to underlying triggers, such as sepsis.

Question 81

What criteria are required for diagnosing DKA?

Answer 81

To diagnose DKA, the patient must exhibit hyperglycaemia (blood glucose > 11 mmol/l), ketosis (blood ketones > 3 mmol/l), and acidosis (pH < 7.3).

Question 82

What are the principles of DKA management in children?

Answer 82

The two pillars of DKA correction are evenly correcting dehydration over 48 hours and administering a fixed-rate insulin infusion to switch off ketone production. Other principles include avoiding fluid boluses, treating underlying triggers, preventing hypoglycaemia, and monitoring for cerebral oedema.

Question 83

Why is it important to avoid rapid correction of dehydration in DKA?

Answer 83

Rapid correction of dehydration in DKA increases the risk of cerebral oedema. The goal is to correct dehydration evenly over 48 hours to reduce the risk of complications.

Question 84

What steps are involved in managing DKA in children?

Answer 84

Managing DKA involves correcting dehydration evenly over 48 hours, administering a fixed-rate insulin infusion, avoiding fluid boluses, treating underlying triggers, preventing hypoglycaemia, adding potassium to IV fluids, and closely monitoring for signs of cerebral oedema.

Question 85

What are the causes of diabetes mellitus type I?

Answer 85

Diabetes mellitus type I is caused by an autoimmune response involving two components: an environmental component, believed to be an unknown virus infecting specific cells, and an immune component, where the immune system reacts inappropriately due to susceptibility genes (HLA-DR3 and HLA-DR4), leading to the production of antibodies attacking pancreatic beta cells.

Question 86

Describe the environmental component in diabetes type I.

Answer 86

The environmental component in diabetes type I is an unknown virus that infects specific cells. Viral proteins expressed onto MCH-1 complexes in those cells trigger a cytotoxic T-cell immune response, generating an immune response against it.

Question 87

Explain the role of susceptibility genes in diabetes type I.

Answer 87

Susceptibility genes (HLA-DR3 and HLA-DR4) in diabetes type I lead to an inappropriate immune response. T-cells release cytokines, stimulating plasma cells to produce antibodies. These genes are associated with other autoimmune diseases, and the antibodies attack specific portions of cells, such as pancreatic beta cells.

Question 88

Which antibodies are associated with diabetes mellitus type I?

Answer 88

Three sets of antibodies are associated with diabetes type I: anti-islet cell antibodies (target self-antigens on pancreatic islet cells), anti-glutamic acid antibodies (target glutamic acid decarboxylase), and anti-insulin antibodies (target insulin). These antibodies contribute to the destruction of beta cells.

Question 89

How does glucose metabolism occur in beta cells?

Answer 89

Glucose enters beta cells via a glucose transporter (GLUT) and undergoes aerobic metabolism, producing ATP. ATP molecules bind to K+ sensitive channels, leading to insulin release.

Question 90

Describe the role of glutamic acid decarboxylase in beta cells.

Answer 90

Glutamic acid decarboxylase converts glutamic acid into GABA, a molecule associated with stimulating insulin production and having protective effects on beta cells.

Question 91

What happens if insulin production is decreased in diabetes type I?

Answer 91

Insulin binds to insulin receptors on different cells, triggering an intracellular cascade that increases the expression of glucose transporters on the cell membrane. If insulin production is decreased, this cascade is compromised, leading to impaired glucose entry into cells.

Question 92

How does insulin affect different cells in the body?

Answer 92

Insulin binds to insulin receptors on different cells, triggering an intracellular cascade that increases the expression of glucose transporters on the cell membrane. This allows glucose to enter the cell, facilitating various cellular processes.

Question 93

Explain the role of anti-islet cell antibodies in diabetes type I.

Answer 93

Anti-islet cell antibodies target specific self-antigens on pancreatic islet cells, contributing to the destruction of these cells in diabetes type I.

Question 94

What are the effects of anti-glutamic acid antibodies in diabetes type I?

Answer 94

Anti-glutamic acid antibodies target glutamic acid decarboxylase, a crucial enzyme in beta cells. This antibody action contributes to the destruction of beta cells in diabetes type I.

Question 95

How does insulin binding to insulin receptors impact cells?

Answer 95

Insulin binding to insulin receptors triggers an intracellular cascade that increases the expression of glucose transporters on the cell membrane. This allows glucose to enter the cell, facilitating various cellular processes. If insulin production is decreased, this cascade is compromised, leading to impaired glucose entry into cells.

Question 96

What is believed to be responsible for diabetes type II?

Answer 96

Metabolic syndrome is believed to be responsible for diabetes type II. Metabolic syndrome is diagnosed with 3 or more of the following signs and symptoms: fasting glucose level ≥ 100mg/dl, triglycerides ≥ 150mg/dl, HDL ≤ 50 (females) and 40 (males), blood pressure ≥ 130/85 mmHg, BMI ≥ 35 (females) and 40 (males). Genetic components and certain ethnicities, like Pacific islanders, are also associated with a high risk of insulin resistance.

Question 97

Explain the genetic components associated with diabetes type II.

Answer 97

Research suggests that having a first-degree relative and certain ethnicities, particularly Pacific islanders, are high-risk genetic components for insulin resistance and diabetes type II.

Question 98

How does glucose metabolism occur in beta cells?

Answer 98

Glucose enters beta cells via a glucose transporter, undergoes aerobic metabolism, and produces ATP. These ATP molecules bind to K+ sensitive channels, triggering insulin release.

Question 99

Describe the role of glutamic acid decarboxylase in beta cells.

Answer 99

Glutamic acid decarboxylase, an enzyme in beta cells, converts glutamic acid into GABA. GABA is associated with stimulating insulin production and has protective effects on beta cells.

Question 100

What happens to beta cell activity over time in diabetes type II?

Answer 100

In diabetes type II, there is a decreased intracellular response to insulin, making it challenging to get glucose into the cells. Over time, beta cells decrease their activity. Another protein released alongside insulin is amylin, which accumulates around beta cells, causing amyloid deposition, damaging the cells, and further decreasing their activity.

Question 101

How does hyperglycemia affect the kidneys in diabetes type II?

Answer 101

Hyperglycemia in diabetes type II causes a large amount of glucose to be filtered into the kidney tubules through glomerular filtration, resulting in glycosuria. The kidney tubules can't reabsorb such amounts of glucose, leading to polyuria. Glucose, being osmotically active, pulls water with it, causing polydipsia. Hyperosmolar blood, with low water and high glucose, stimulates osmoreceptors, triggering an increase in thirst (polydipsia).

Question 102

What metabolic changes occur in response to decreased glucose utilization in diabetes type II?

Answer 102

Decreased glucose utilization leads to decreased ATP production. The body is forced to use other metabolic sources of fuel, including lipolysis in the adipose tissue (breakdown of triglycerides into free fatty acids and glycerol) and proteolysis in the muscles (breakdown of proteins into amino acids). Increased lipolysis and proteolysis result in unexplained weight loss, known as polyphagia, as the body tries to replenish the calories.

Question 103

Explain the diagnostic criteria for diabetes mellitus using blood work.

Answer 103

Fasting glucose ≥ 126mg/dl indicates diabetes, especially if the patient hasn't eaten for a certain amount of time. Random glucose ≥ 200 mg/dl, regardless of eating or fasting, alongside other symptoms is diagnostic of diabetes. In a 2-hour oral glucose tolerance test, glucose ≥ 200 mg/dl after administration indicates diabetes. Hemoglobin A1c ≥ 6.5% is used for diagnosis and monitoring glucose control over three months. Antibodies such as anti-islet cell antibodies, anti-glutamic acid antibodies, and anti-insulin antibodies should also be considered based on age and risk factors.

Question 104

What is the significance of Hemoglobin A1c in diabetes diagnosis and monitoring?

Answer 104

Hemoglobin A1c ≥ 6.5% is used for the diagnosis and monitoring of glucose control over three months. High blood glucose levels make glucose conjugate to hemoglobin, producing glycated hemoglobin. It reflects the average blood glucose level over the lifespan of red blood cells (three months).

Question 105

Describe non-enzymatic glycation and its effects on blood vessels.

Answer 105

Non-enzymatic glycation occurs when high blood glucose levels make glucose conjugate with different molecules, mainly proteins and lipids, without using enzymes. This process creates potent inflammatory molecules that can cause inflammation of the blood vessels, leading to atherosclerosis and hyaline arteriolosclerosis. The combination of these effects results in decreased blood flow distal to plaques and arterioles, reduced gas exchange across tissues due to thickened basal membranes, and physical manifestations of certain diseases associated with non-enzymatic glycation.

Question 106

What complications can arise from atherosclerosis in diabetes?

Answer 106

Within the vessels in the heart, atherosclerosis can lead to coronary artery disease, potentially resulting in myocardial infarction. In the vessels of the lower extremities, it can lead to peripheral artery disease, presenting with claudication and decreased blood flow to the tissues. In vessels supplying nervous tissue, atherosclerosis can lead to an ischemic stroke. In the vessels of the retina, it can cause retinopathy, characterized by microaneurysms, cotton wool spots, and flame hemorrhages, affecting vision.

Question 107

How does hyaline arteriolosclerosis contribute to kidney damage in diabetes?

Answer 107

Hyaline arteriolosclerosis within the vessels of the glomeruli damages the glomeruli, leading to the leakage of albumin into the urine, known as microalbuminuria. Consistent microalbuminuria over time can progress to chronic kidney disease, making it the most common cause of chronic kidney disease. The proteinaceous deposits formed within the glomeruli are referred to as Kimmelstiel-Wilson nodules.

Question 108

Explain the process of osmotic cell death in diabetes.

Answer 108

Glucose taken up into cells can be converted to sorbitol by aldose reductase. Sorbitol is further converted into fructose by sorbitol dehydrogenase. Certain tissues lack sorbitol dehydrogenase, leading to the accumulation of osmotically active sorbitol that pulls water into cells, causing osmotic cell death. This process occurs in various tissues, such as the lens of the eye (leading to cataracts), the cells of the proximal convoluted tubule or other tubular cells (contributing to nephropathy progression), and Schwann cells of peripheral nerves (resulting in demyelination affecting autonomic, peripheral, and somatic nerves).

Question 109

What is the first-line treatment for diabetes type 1?

Answer 109

Diabetes type 1 is treated with insulin.

Question 110

How is diabetes type 2 managed regarding weight loss?

Answer 110

For diabetes type 2, weight loss is promoted through exercise and dietary changes. This is particularly important as type 2 diabetes is associated with metabolic syndrome, and patients are often obese with poor diets.

Question 111

What is the first-line medication for diabetes type 2?

Answer 111

Metformin is the first-line medication for diabetes type 2.

Question 112

Name some other medications used for diabetes type 2.

Answer 112

Other medications for diabetes type 2 include GLP-1 agonists, DPP-4 inhibitors, SGLT2 inhibitors, thiazolidinediones, sulfonylureas, glucosidase inhibitors, and meglitinides. In some cases, insulin may be given if patients are on multiple diabetes medications and their hemoglobin A1c is greater than 7%.

Question 113

What are the first-line medications for neuropathy in diabetes?

Answer 113

For neuropathy in diabetes, gabapentin and pregabalin are first-line medications. They help decrease numbness, pain, and tingling.

Question 114

How is nephropathy in diabetes treated?

Answer 114

ACE inhibitors and ARBs are the first-line medications for nephropathy in diabetes. They help decrease proteinuria. Monitoring kidney function, checking the basic metabolic panel (BMP) for increased creatinine and blood urea nitrogen, and monitoring the amount of albumin in the urine are essential in managing nephropathy.

Question 115

What is the first-line medication for retinopathy in diabetes?

Answer 115

Vascular endothelial growth factor inhibitors (VEGF inhibitors) are the first-line medication for retinopathy in diabetes. Other interventions include laser photocoagulation and vitrectomy. Regular yearly optometry visits are crucial for monitoring retinopathy.

Question 116

How is atherosclerosis managed in diabetes?

Answer 116

Aspirin is used as a prophylactic measure for atherosclerosis. If the atherosclerotic disease risk is very high (≥7.5%), lipid panels are monitored, and statins may be given to reduce the risk of complications.

Question 117

What is the target Hemoglobin A1c level for glucose control in diabetes?

Answer 117

Hemoglobin A1c (HbA1c) should be kept below 7% for glucose control in diabetes. Uncontrolled HbA1c (>7%) should be checked every 3 months, while well-controlled HbA1c (≤7% or less) should be checked every 6 months.