Diabetes Mellitus Flashcards
1
Q
What hormones are produced by the pancreas, and by which cells?
A
- Insulin by β cells.
- Glucagon by α cells.
- Somatostatin by δ cells.
2
Q
What are the primary functions of insulin?
A
Carbohydrates:
1. Increases glucose uptake.
2. Increases glycogen synthesis (storage).
3. Decreases gluconeogenesis.
4. Increases glycolysis (muscle).
5. Increases conversion of carbohydrates to fat (lipogenesis).
Fats:
1. Decreases lipolysis (fat breakdown).
Proteins:
1. Increases amino acid uptake.
2. Increases protein synthesis.
It ultimately results in decreased blood glucose.
3
Q
What is the primary function of glucagon?
A
Regulates blood glucose by promoting glycogen breakdown and glucose release from the liver.
It ultimately results in increased blood glucose.
4
Q
What is the role of somatostatin in the pancreas?
A
Inhibits the release of insulin and glucagon and regulates the endocrine system.
5
Q
What complications arise from a lack of insulin?
A
Severe hyperglycemia, leading to retinopathy, nephropathy, neuropathy, and cardiovascular complications.
6
Q
How is diabetes mellitus (DM) characterized?
A
As a group of heterogeneous syndromes causing elevated blood glucose and insufficient insulin secretion.
7
Q
What are the four clinical classifications of diabetes?
A
- Type 1: Insulin-dependent.
- Type 2: Non-insulin-dependent.
- Gestational diabetes.
- Diabetes due to other factors (such as genetic defects, pancreatic disorders, or medications).
8
Q
Why doesn’t Type 1 diabetes respond to oral hypoglycemic drugs?
A
Because it requires exogenous insulin due to absolute insulin deficiency.
9
Q
How is Type 2 diabetes managed, and what may be required in late-stage disease?
A
Managed with oral hypoglycemic agents (OHAs); insulin may be required in late-stage disease.
10
Q
Who is more likely to develop gestational diabetes?
A
Obese pregnant women.
11
Q
What are some causes of diabetes due to other factors?
A
Drugs like thiazides and loop diuretics, diseases (e.g., pancreatitis), and chemicals like alloxan and streptozotocin.
12
Q
When is Type 1 diabetes most commonly diagnosed?
A
During puberty or early adulthood.
13
Q
What causes the absolute deficiency of insulin in Type 1 diabetes?
A
Massive β-cell necrosis.
14
Q
What mediates the autoimmune process in Type 1 diabetes?
A
An autoimmune process directed against β-cells, possibly due to virus invasion or chemical toxins.
15
Q
What are the common symptoms of Type 1 diabetes?
A
- Polydipsia (excessive thirst).
- Polyphagia (excessive hunger).
- Polyuria (frequent urination).
- Weight loss.
16
Q
What life-threatening condition is associated with Type 1 diabetes?
A
Ketoacidosis.
17
Q
What is ketoacidosis and how does it relate to Type 1 diabetes?
A
Ketoacidosis is a life-threatening condition where high blood sugar leads to the production of ketones, causing blood acidity. It occurs in Type 1 diabetes due to insufficient insulin.
18
Q
Compare the effects of insulin between people without diabetes and those with diabetes.
A
Normally, in patients without diabetes, constant β-cell secretion maintains low basal levels of circulating insulin. This suppresses:
- Lipolysis (breakdown of fats into fatty acids and glycerol).
- Proteolysis (breakdown of proteins into amino acids.
- Glycogenolysis (breakdown of glycogen into glucose).
Without insulin:
- Increased lipolysis leads to elevated levels of free fatty acids in the blood, contributing to ketoacidosis.
- Increased proteolysis results in muscle wasting and elevated amino acid levels in the blood, contributing to gluconeogenesis and further raising blood glucose levels.
- Increased glycogenolysis leads to elevated blood glucose levels, contributing to hyperglycemia.
19
Q
What is HbA1c and how does it relate to Type 1 diabetes management?
A
HbA1c, or glycated hemoglobin, measures the average blood glucose levels over the past 2-3 months. In Type 1 diabetes, maintaining accepted HbA1c levels helps control hyperglycemia and ketoacidosis, preventing long-term complications.
20
Q
Why is exogenous insulin necessary for Type 1 diabetes patients?
A
To control hyperglycemia and ketoacidosis and maintain accepted HbA1c levels to avoid long-term complications.
21
Q
What is a significant limitation of β-cells in Type 1 diabetes?
A
They cannot maintain normal insulin secretion or respond to variations in circulating glucose and amino acids.
22
Q
Describe insulin secretion after the ingestion of a meal.
A
A burst of insulin secretion occurs within 2 minutes after ingesting a meal, in response to transient increases in circulating glucose and amino acids. This lasts for up to 15 minutes, followed by the postprandial secretion of insulin.
Without functional β cells, those with type 1 diabetes can neither maintain basal secretion of insulin nor release a bolus of insulin to respond to variations in circulating glucose.
23
Q
What is the most common type of diabetes?
A
Type 2 diabetes.
24
Q
What factors influence Type 2 diabetes?
A
- Genetic factors.
- Aging.
- Obesity.
- Peripheral insulin resistance.
25
How do the metabolic alterations in Type 2 diabetes compare to Type 1?
They are milder in Type 2 diabetes.
26
Does ketoacidosis occur in Type 2 diabetes?
No.
27
What is the status of β-cell function in Type 2 diabetes?
The pancreas retains some β-cell function, but insulin secretion is variable and insufficient for glucose homeostasis.
28
What is the major cause of Type 2 diabetes?
Lack of sensitivity of target organs to insulin.
29
What is the treatment goal for Type 2 diabetes?
To prevent long-term complications.
30
What happens to β-cell function as Type 2 diabetes progresses?
β-cell function declines, and insulin therapy may be required to maintain satisfactory serum glucose levels.
31
Why can't insulin be taken orally?
It is degraded in the GIT due to it being a polypeptide hormone, so it must be administered by subcutaneous injection.
32
What is the precursor of insulin?
Pro-insulin, which is inactive and undergoes proteolytic cleavage to form insulin and C peptide, both of which are secreted by β cells of the pancreas.
33
Why is measuring C peptide levels a better index of insulin levels?
Because insulin undergoes significant hepatic and renal extraction, plasma insulin levels may not accurately reflect insulin production.
C peptide is secreted in equimolar amounts with insulin, providing a more accurate measure of endogenous insulin secretion.
34
What are the main regulators of insulin secretion?
Blood glucose (most important), certain amino acids, gastrointestinal hormones, and autonomic mediators.
35
How does glucose intake lead to insulin secretion in the pancreas?
Glucose is phosphorylated by glucokinase, producing glucose-6-phosphate. This leads to an increase in ATP production, which inhibits potassium efflux by closing ATP-sensitive potassium channels, causing depolarization. This depolarization opens voltage-gated calcium channels, increasing intracellular calcium, which triggers insulin secretion.
36
What are the effects of insulin on carbohydrates?
Insulin increases glucose uptake, glycogen synthesis, glycolysis, and lipogenesis; and decreases gluconeogenesis.
Glycogen Synthesis: Formation of glycogen from glucose.
Glycolysis: Breakdown of glucose to produce energy.
Lipogenesis: Conversion of glucose into fatty acids and triglycerides.
Gluconeogenesis: Production of glucose from non-carbohydrate sources.
37
What are the effects of insulin on fat and protein metabolism?
Insulin decreases lipolysis and increases amino acid uptake for protein synthesis.
Lipolysis: The breakdown of triglycerides into glycerol and free fatty acids. This process releases stored energy from fat cells and is inhibited by insulin.
38
Why do insulin preparations vary in onset and duration of activity?
Due to differences in amino acid sequences of the polypeptides and the type of formulation.
39
Why do lispro, aspart, and glulisine have a faster onset and shorter duration than regular insulin?
They do not aggregate or form complexes.
40
What is the characteristic of long-acting insulins like glargine and detemir?
They show prolonged, flat levels of the hormone following injection (i.e., they maintain steady insulin levels without peaks, providing consistent glucose control over a long period.)
41
What is the most serious and common adverse reaction to an overdose of insulin?
Hypoglycemia.
42
What are some other adverse reactions to insulin besides hypoglycemia?
1. Weight gain.
2. Lipodystrophy (less common with human insulin).
3. Allergic reactions.
4. Local injection site reactions.
43
Which insulin preparations are considered rapid-acting and short-acting?
- Regular insulin.
- Insulin lispro.
- Insulin aspart.
- Insulin glulisine.
44
Which type of insulin can be given IV in emergencies?
Regular insulin.
45
What is the advantage of rapid-acting insulins like lispro over regular insulin?
They are absorbed more rapidly, leading to quicker action.
46
Which insulin has the lowest risk of lipodystrophy?
Regular insulin.
47
Why are rapid-acting insulins usually administered?
To mimic the mealtime (prandial) release of insulin.
48
When are rapid-acting insulins typically administered?
Immediately before or following a meal.
49
What does Pregnancy Category B mean for insulin?
It indicates that animal studies have not shown risk to the fetus, but there are no well-controlled studies in pregnant women.
50
How do rapid-acting insulins like lispro compare to regular insulin in terms of absorption?
Rapid-acting insulins have more rapid absorption after subcutaneous injection, leading to quicker action.
51
What is another name for Neutral Protamine Hagedorn (NPH) insulin, an intermediate-acting insulin?
Insulin isophane.
52
How should intermediate-acting insulin (NPH) be administered?
Subcutaneously, never intravenously, due to it being a suspension.
53
Why does NPH insulin have a delayed absorption?
It forms a less-soluble complex with protamine, delaying absorption and resulting in an intermediate duration of action (it has neutral pH with a positively charged polypeptide).
54
For which conditions is intermediate-acting insulin NOT useful?
Diabetic ketoacidosis and emergency hyperglycemia.
55
With what type of insulin is intermediate-acting insulin usually given?
Rapid-acting or short-acting insulin for mealtime control.
56
What is neutral protamine lispro (NPL) insulin used for?
It is used only in combination with insulin lispro.
57
What are some premixed combinations of human insulins?
70% NPH plus 30% regular insulin, 50% of each, OR... 75% NPL plus 25% insulin lispro.
58
Why does the long-acting insulin glargine have an extended action?
Its isoelectric point is lower than human insulin, causing it to precipitate at the injection site.
59
How does the onset of insulin glargine compare to NPH insulin?
Insulin glargine has a slower onset than NPH insulin.
60
What is unique about the hypoglycemic effect of insulin glargine?
It is prolonged and has no peak (flat).
61
How must insulin glargine be administered?
Subcutaneously.
62
What feature of insulin detemir enhances its association to albumin?
It has a fatty-acid side chain.
63
How does the dissociation of insulin detemir from albumin affect its properties?
Slow dissociation results in long-acting properties similar to those of insulin glargine.
64
What is amylin?
Amylin is a hormone that is cosecreted with insulin from β cells following food intake.
It delays gastric emptying, decreases postprandial glucagon secretion, and improves satiety.
65
What is pramlintide?
A synthetic amylin analog.
66
For what is pramlintide indicated?
As an adjunct to mealtime insulin therapy in Type 1 or Type 2 diabetes.
67
What are the effects of pramlintide on gastric emptying and glucagon secretion?
It delays gastric emptying and decreases postprandial glucagon secretion.
68
How is pramlintide administered?
By subcutaneous injection.
69
Why should pramlintide be injected immediately prior to meals?
To effectively delay gastric emptying and decrease postprandial glucagon secretion.
70
Why should the dose of rapid-acting or short-acting insulin be decreased by 50% when initiating pramlintide?
To avoid a risk of severe hypoglycemia.
71
What are the main adverse effects of pramlintide?
Gastrointestinal issues such as nausea, anorexia, and vomiting.
72
Which patients should not be given pramlintide?
Patients with diabetic gastroparesis and those with a history of hypoglycemic unawareness.
73
What do sulfonylureas promote?
Insulin release from the β cells of the pancreas.
74
How do sulfonylureas stimulate insulin release?
By blocking ATP-sensitive K+ channels, causing depolarization and Ca2+ influx, which may cause hypoglycemia.
75
What effect do sulfonylureas have on hepatic glucose production?
They reduce hepatic glucose production.
76
How do sulfonylureas affect peripheral insulin sensitivity?
They increase peripheral insulin sensitivity.
77
What is the first-generation sulfonylurea with the shortest action?
Tolbutamide.
78
What are the second-generation sulfonylurea derivatives with longer durations of action?
Glyburide, glipizide, and glimepiride.
79
Which second-generation sulfonylurea is considered a reasonably safe alternative to insulin therapy for diabetes in pregnancy?
Glyburide.
80
What are common adverse effects of sulfonylureas?
1. Weight gain.
2. Hypoglycemia.
3. Renal impairment is a particular problem with some sulfonylureas, because agents metabolized to active compounds, such as glyburide, can accumulate and cause adverse effects.
81
Why is renal impairment a particular problem with some sulfonylureas?
Because agents metabolized to active compounds, such as glyburide, can accumulate and cause adverse effects.
82
What is required for meglitinide analogs to be effective?
Functioning pancreatic β cells.
83
How do meglitinides work (mechanism of action)?
They bind to a distinct site on the sulfonylurea receptor of ATP-sensitive K+ channels, initiating insulin release.
84
What is the onset and duration of action for meglitinides compared to sulfonylureas?
Meglitinides have a rapid onset and a short duration of action.
85
When are meglitinides particularly effective?
In the early release of insulin after a meal, acting as postprandial glucose regulators.
86
How does the risk of hypoglycemia with meglitinides compare to sulfonylureas?
Hypoglycemia appears to be lower with meglitinides.
87
Why should meglitinides not be used in combination with sulfonylureas?
Because it can cause severe hypoglycemia.
88
Which agents are included in the meglitinide class?
Repaglinide and nateglinide.
89
How do CYP3A4 inhibitors affect repaglinide?
CYP3A4 Inhibitors: Ketoconazole, erythromycin, and clarithromycin.
They enhance the effect of repaglinide and must be used with caution in hepatic impairment.
90
How do CYP3A4 inducers affect repaglinide?
CYP3A4 Inducers: Barbiturates, carbamazepine, and rifampin.
They decrease the effect of repaglinide.
91
How does weight gain with meglitinides compare to sulfonylureas?
Weight gain is less of a problem with meglitinides than with sulfonylureas.
92
What is the only drug member of the biguanides?
Metformin.
93
How does metformin decrease insulin resistance?
By increasing glucose uptake by target tissues.
94
What does metformin require for its action?
Insulin.
95
Does metformin promote insulin secretion?
No.
96
What are the main mechanisms of action of metformin?
1. Inhibits hepatic gluconeogenesis.
2. Slows intestinal absorption of sugars.
3. Improves peripheral glucose uptake and utilization.
4. Reduces LDL and VLDL, and increases HDL.
97
How long do the lipid effects of metformin take to manifest?
4 to 6 weeks of use.
98
Why do patients often lose weight when taking metformin?
Because of loss of appetite.
99
What is the drug of choice for Type 2 diabetics?
Metformin.
100
How is metformin excreted?
It is excreted unchanged renally.
101
Why is metformin effective in treating polycystic ovary disease (PCOS)?
It lowers insulin resistance, which can result in ovulation and possibly pregnancy.
102
What are the adverse effects of metformin?
Gastrointestinal disturbance.
103
In which conditions is metformin contraindicated?
Renal and hepatic disease, acute MI and CHF, severe infection, and diabetic ketoacidosis.
104
Why is metformin contraindicated in renal and hepatic disease?
Because impaired renal or hepatic function can increase the risk of lactic acidosis.
105
What potential issue can arise from the long-term use of metformin?
It may interfere with vitamin B12 absorption.
106
Why is hypoglycemia less common with metformin than with sulfonylureas?
Because metformin does not promote insulin secretion.
107
What is required for the action of thiazolidinediones (glitazones)?
Insulin.
108
Do thiazolidinediones promote insulin secretion?
No.
109
What are two members of the thiazolidinediones class?
Pioglitazone and rosiglitazone.
110
What is the mechanism of action of thiazolidinediones?
They target the peroxisome proliferator-activated receptor (PPARγ), regulating fat and glucose metabolism, and increasing insulin sensitivity in adipose tissue, liver, and skeletal muscle.
111
How does pioglitazone affect LDL levels?
LDL is not affected by pioglitazone.
112
How does rosiglitazone affect LDL levels and what are the associated risks?
LDL levels increase with rosiglitazone, leading to cardiovascular toxicity and water retention.
113
How do thiazolidinediones (TZDs) affect HDL levels?
HDL increases with both pioglitazone and rosiglitazone.
114
What is a common side effect of thiazolidinediones regarding fat distribution?
They cause redistribution of fat from visceral to subcutaneous tissues, leading to weight gain.
115
When are thiazolidinediones (glitazones) recommended?
As a second-line alternative for patients who fail or have contraindications to metformin therapy.
116
How are glitazones absorbed?
They are absorbed well from the GIT.
117
Should glitazones be used in nursing mothers?
No.
118
How do glitazones affect women with polycystic ovary syndrome (PCOS)?
They relieve insulin resistance, causing ovulation to resume in premenopausal women.
119
Why might women taking oral contraceptives and TZDs become pregnant?
Because TZDs have been shown to reduce plasma concentrations of the estrogen-containing contraceptives.
120
What are the adverse effects associated with glitazones?
1. Low incidence of liver toxicity.
2. Weight gain.
3. Osteopenia and increased fracture risk.
4. Increased risk of myocardial infarction and death.
121
What is α-glucoside?
An enzyme responsible for the hydrolysis of oligosaccharides to glucose.
122
What is α-amylase?
α-amylase is an enzyme that facilitates digestion of polysaccharides and contributes to elevated blood glucose levels and postprandial hyperglycemia.
123
Give two examples of α-glucoside inhibitors.
Acarbose.
Miglitol.
124
Which type of diabetes are α-glucoside inhibitors used for?
Type 2 diabetes.
125
Why are α-glucoside inhibitors taken at the beginning of meals?
They delay the digestion of carbohydrates, thereby resulting in lower postprandial glucose levels.
126
What is the mechanism of action of α-glucoside inhibitors?
1. Reversible inhibition of α-glucoside in the intestinal brush border.
2. Inhibition of pancreatic α-amylase.
127
How is acarbose absorbed?
Poorly.
128
How is miglitol absorbed?
Very well absorbed, but it has no systemic effects.
129
What are the major side effects of α-glucoside inhibitors?
1. Flatulence.
2. Diarrhea.
3. Abdominal cramping.
130
Who should NOT use α-glucoside inhibitors?
Patients with inflammatory bowel disease, colonic ulceration, or intestinal obstruction.
131
How do DDP-IV inhibitors work?
By orally inhibiting DDP-IV enzyme.
132
What is DDP-IV enzyme?
DDP-IV is an enzyme which is responsible for the inactivation of incretin hormones, such as GLP-1.
133
What is an example of a DDP-IV inhibitors?
Sitagliptin.
134
How does sitagliptin work?
By preventing incretin hormone inactivation, it results in increased insulin release in response to meals and reduces inappropriate secretion of glucagon.
135
How is sitagliptin absorbed?
Absorbed well after oral administration.
136
How is sitagliptin excreted?
Sitagliptin type of drug is excreted unchanged in the urine, so dosage should be adjusted appropriately for patients with renal dysfunction.
137
What are the most common adverse effects of DDP-IV inhibitors?
1. Nasopharyngitis.
2. Headaches.
138
What is the risk of hypoglycemia with DDP-IV inhibitors?
Very rare.
139
What are incretins?
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.
140
What is an example of incretin mimetics?
Exenatide.
141
What is the incretin effect?
Oral glucose results in a higher secretion of insulin than occurs when an equal load of glucose is given intravenously. This effect is reduced in Type 2 diabetes.
142
When should exenatide be administered?
Before meals.
143
How does exenatide work?
By:
1. Improving glucose-dependent insulin secretion.
2. Slowing gastric emptying time.
3. Decreasing food intake.
4. Decreases postprandial glucose secretion.
5. Promotes β cell proliferation.
Consequently, weight gain and postprandial hyperglycemia are reduced, and HbA1c levels decline.
144
How is exenatide given?
It is administered subcutaneously, never orally, due to it being a polypeptide.
145
What are the side effects of exenatide?
Similar to pramlintide, it causes GIT effects, such as:
1. Nausea.
2. Vomiting.
3. Diarrhea.
146
Give two examples of SGLT2 inhibitors.
1. Canagliflozin.
2. Dapagliflozin.
147
For which type of diabetes are SGLT2 inhibitors used?
Type 2 diabetes.
148
How do SGLT2 inhibitors work?
SGLT2 is responsible for reabsorbing filtered glucose in the tubular lumen of the kidney. By inhibiting it, these agents decrease reabsorption of glucose by increasing urinary glucose secretion. This ultimately lowers blood glucose.
149
How does SGLT2 inhibitors affect blood pressure?
Beside decreasing glucose reabsorption, they also decrease reabsorption of sodium. The increased excretion of sodium causes osmotic diuresis, which reduces systolic blood pressure.
150
Are SGLT2 inhibitors indicated for treating hypertension?
No.
151
What are the side effects associated with SGLT2 inhibitors?
Female genital mycotic infections (vulvovaginal candidiasis) and urinary tract infections.
