Pancreatic Islets & Physiology of Diabetes Flashcards
(218 cards)
1
Q
DKA Case (Mathias, 18 y/o)
A
Dx:
🩺 Diabetic Ketoacidosis (DKA)
Trigger:
🔥 Infection (Left lower lobe pneumonia)
Key Clues:
Type 1 DM, stopped controlling glucose
Polyuria, thirst, fever, cough
Kussmaul breathing (RR 32), dry lips
Glucose: 600 mg/dL, Urine: 4+ glucose, large ketones
CXR: Lung opacity
Vitals:
BP ↓ 90/60 (shock)
HR ↑ 105 (tachycardia)
Temp ↑ 38°C (fever)
RR ↑ 32 (deep, rapid breathing = acidosis)
Cause of Hyperglycemia:
❌ Autoimmune β-cell destruction → ↓ insulin
2
Q
T2DM Case (Anthony, 35 y/o)
A
Dx:
🩺 Type 2 Diabetes Mellitus
Dyslipidemia (↑ TG 361 mg/dL)
Early NAFLD (SGPT ↑ 105)
Clues:
Nocturia
Overweight, poor diet
Acanthosis nigricans
FBS: 261 mg/dL, HbA1c: 9.0%
Cause of Hyperglycemia:
❌ Insulin resistance (cells ignore insulin)
3
Q
GDM Case (Isabel, 26 wks preg)
A
Dx:
👩🍼 Gestational Diabetes Mellitus (GDM)
Clues:
PCOS, hx of GDM, LGA baby
OGTT: FBS: 99, 1h: 186, 2h: 162
Meets IADPSG criteria
Cause of Hyperglycemia:
🧬 hPL-induced insulin resistance + inadequate insulin response
Complications:
👩🍼 Mom: recurrent GDM, future T2DM
👶 Baby: hypoglycemia, RDS, obesity, T2DM later
4
Q
Endocrine spherical or ovoid clusters in the pancreas, scattered among exocrine acini (~1 million islets, 1–2% of pancreatic mass)
A
Islets of Langerhans
5
Q
Blood Supply of Islets
A
Rich capillary network for hormone release directly into the bloodstream
6
Q
Islet Location Tip
A
“Islands” of endocrine tissue in a “sea” of exocrine pancreas
7
Q
What do Beta (β) cells secrete?
A
Insulin – lowers blood glucose by promoting uptake and storage
8
Q
What percentage of islet cells are Beta (β) cells?
A
~70%
9
Q
What is the structure of insulin?
A
Polypeptide, ~3500 Da
10
Q
What do Alpha (α) cells secrete?
A
Glucagon – raises blood glucose by stimulating glycogenolysis
11
Q
What percentage of islet cells are Alpha (α) cells?
A
~20%
12
Q
What is the structure of glucagon?
A
Dimer with S–S bridges, ~5700–6000 Da
13
Q
What do Delta (δ) cells secrete?
A
Somatostatin – inhibits insulin, glucagon, and GH secretion
14
Q
What percentage of islet cells are Delta (δ) cells?
A
~5–10%
15
Q
What is the structure of somatostatin?
A
Polypeptide, ~1650 Da
16
Q
What do PP (F) cells secrete?
A
Pancreatic Polypeptide – regulates pancreatic exocrine and GI functions
17
Q
How common are PP (F) cells in the islets?
A
Rare
18
Q
What is the structure of pancreatic polypeptide?
A
Polypeptide, ~4200 Da
19
Q
What is the BAG-P mnemonic for pancreatic islet cells?
A
Beta – Insulin – ↓ Glucose
Alpha – Glucagon – ↑ Glucose
Gamma (Delta) – Somatostatin – Generic inhibitor
PP cells – Pancreatic Polypeptide – GI & exocrine regulation
20
Q
Where are alpha (α) cells located in the pancreatic islets?
A
In the periphery of the islets.
21
Q
Where are beta (β) cells located in the pancreatic islets?
A
In the center (interior) of the islets.
22
Q
What does an H&E stain show in pancreatic tissue?
A
Islets distinguishable → exocrine tissue;
α and β cells cannot be individually identified without special stains.
23
Q
What is the direction of blood flow in the pancreatic islets?
A
Blood enters CENTRALLY (near β cells) and flows OUTWARD to the α cells.
24
Q
Why is islet blood flow directed from center to periphery?
A
So that β cells detect increased glucose first and can rapidly secrete insulin
25
What percentage of the pancreas is made up of exocrine tissue?
98–99%
26
What percentage of the pancreas is made up of endocrine islets (Islets of Langerhans)?
Only 1–2% of the total mass.
27
How are pancreatic islets distributed within the pancreas?
They are scattered throughout the pancreas.
28
How do islets appear on H&E stain compared to exocrine tissue?
As lighter-staining clusters within the darker exocrine acini.
29
(5) Endocrine Functions of the Pancreas
REGULATES
1. blood glucose
🩸 insulin (↓ glucose)
🩸 glucagon (↑ glucose)
2. 🍞 carbohydrate & lipid metabolism
3. GI motility
🌀 minor hormones (e.g., somatostatin, pancreatic polypeptide)
4. 💧 GI secretions
MODULATES
5. 🔄 other endocrine glands (e.g., through somatostatin’s inhibitory effects)
30
It is a primary anabolic hormone that lowers blood glucose and free fatty acids.
Insulin
31
Why is glucose regulation critical?
Very low glucose = fatal
Uncontrolled glucose = long-term complications.
32
What type of hormone is insulin?
A protein/peptide hormone (same family as IGF-I/II and relaxin).
33
Where is preproinsulin synthesized?
ribosomes of β-cells.
34
What happens to preproinsulin in the ER?
Cleaved into proinsulin by removing the N-terminal signal.
35
Components of Proinsulin
Insulin + C-peptide, connected by disulfide bonds.
36
Where is proinsulin processed into insulin?
In the Golgi apparatus, using proteases.
37
What is stored in secretory granules of β-cells?
Insulin and C-peptide → ready for release upon stimulation.
38
Why is C-peptide clinically important?
It is used to assess endogenous insulin production since exogenous insulin lacks C-peptide.
39
What triggers insulin release from secretory granules?
High blood glucose or other stimuli that signal β-cells.
40
What is the primary stimulus for insulin secretion?
Increased blood glucose from a carbohydrate-rich meal.
41
How does glucose enter pancreatic β-cells?
Through GLUT-2 transporters → act as glucose sensors.
42
What happens to glucose after entering the β-cell?
Undergoes glycolysis in the cytosol → ATP production.
43
How does increased ATP affect K+ channels?
It closes ATP-sensitive K+ channels, preventing K+ efflux.
44
What is the result of K+ channel closure in β-cells?
Depolarization of the β-cell membrane
45
What does depolarization open in the β-cell membrane?
Voltage-gated Ca²⁺ channels, leading to Ca²⁺ influx.
46
What does the influx of Ca²⁺ trigger?
Exocytosis of insulin and C-peptide from secretory granules.
47
What enzyme phosphorylates glucose in β-cells?
Glucokinase (high Km, low affinity)
48
Why is glucokinase used instead of hexokinase in β-cells?
To ensure insulin is only secreted at high glucose levels.
49
What is the first metabolic step of glucose in β-cells?
Glycolysis in the cytosol → ATP production
50
How does increased ATP affect K⁺ channels?
Closes ATP-sensitive K⁺ channels → membrane depolarization
51
What opens due to β-cell depolarization?
Voltage-gated Ca²⁺ channels
52
What triggers insulin exocytosis in β-cells?
Increased intracellular Ca²⁺
53
How do amino acids stimulate insulin secretion?
↑ ATP through metabolism → stimulates insulin release
54
What neurotransmitter enhances insulin via M3 receptors?
Acetylcholine (ACh) → via IP₃ → ↑ intracellular Ca²⁺
55
What GI hormone boosts insulin after meals?
GLP-1 → ↑ cAMP → enhances Ca²⁺ effect
56
How does epinephrine affect insulin secretion via α2 receptors?
Generally inhibits insulin during stress (despite ↑ cAMP pathway)
57
How do free fatty acids (FFAs) influence insulin?
Enhance insulin secretion → energy metabolism
58
What is the primary trigger for insulin secretion?
↑ Blood Glucose via GLUT-2 → ATP ↑ → K⁺ channel closure → Ca²⁺ influx
59
How do amino acids enhance insulin secretion?
Metabolism → ATP ↑ → stimulates insulin release (secondary enhancer)
60
How does acetylcholine (ACh) stimulate insulin secretion?
Activates M3 receptors → IP₃ → Ca²⁺ ↑
61
What hormone from the GI tract enhances insulin after meals?
GLP-1 (Incretin) → ↑ cAMP → enhances Ca²⁺ effect
62
How does epinephrine (via α2 receptors) affect insulin secretion?
Modulatory (can inhibit); ↑ cAMP → PKA → enhances or inhibits Ca²⁺ effect depending on stress level
63
What is the effect of free fatty acids (FFAs) on insulin secretion?
Enhance insulin secretion via metabolism → ATP ↑
64
Primary Stimulus
↑ Blood Glucose (via GLUT-2 & Glucokinase)
65
Secondary Stimuli
Amino Acids
Acetylcholine (ACh)
GLP-1
Free Fatty Acids
Epinephrine/Norepinephrine (α2)
66
What causes the initial spike in insulin secretion after eating?
Release of preformed insulin from β-cells within minutes of glucose rise.
67
Why does the initial insulin spike decline shortly after it occurs?
Depletion and rapid metabolism of preformed insulin.
68
What causes the second, sustained rise in insulin levels after a meal?
Synthesis and release of new insulin due to continued high glucose.
69
When does the second insulin rise typically plateau?
After 2–3 hours, if blood glucose remains elevated.
70
What is the basal insulin level during fasting?
Around 10 µU/mL.
71
How much can insulin secretion increase at very high glucose levels (400–600 mg/dL)?
10–25× the basal level.
72
How quickly does insulin secretion drop after blood glucose returns to normal?
Within 3–5 minutes.
73
What type of feedback mechanism controls insulin secretion?
Negative feedback: High glucose ↑ insulin; low glucose ↓ insulin.
74
Other factors INCREASE insulin secretion
↑ Blood glucose (primary stimulus)
↑ Free fatty acids
↑ Amino acids
Gastrointestinal hormones: gastrin, CCK, secretin, GIP
Other hormones: glucagon, GH, cortisol
Parasympathetic stimulation (via acetylcholine)
β-adrenergic stimulation
Insulin resistance / Obesity
Sulfonylurea drugs (e.g., glyburide, tolbutamide)
75
Other factors DECREASE insulin secretion
↓ Blood glucose / Fasting
Somatostatin (pancreatic hormone)
α-adrenergic activity
Leptin
76
Where is the insulin receptor located?
On the cell membranes of target tissues like liver, muscle, and adipocytes.
77
What type of receptor is the insulin receptor (InsR)?
Receptor Tyrosine Kinase (RTK)
Homodimer
78
What happens when insulin binds to its receptor?
Receptor undergoes cross-phosphorylation (autophosphorylation), activating downstream signaling.
79
What protein is phosphorylated directly by the insulin receptor?
Insulin Receptor Substrate (IRS).
80
What does IRS activate in the insulin signaling pathway?
Phosphoinositide 3-kinase (PI3K).
81
What conversion does PI3K catalyze in the insulin signaling pathway?
Converts PIP2 → PIP3.
82
What is recruited to the membrane by PIP3?
Akt (Protein Kinase B)
83
What transporter is translocated by Akt activation?
GLUT4 → ↑ glucose uptake in muscle and adipose tissue.
84
How does insulin promote glycogen synthesis?
Akt activation → ↑ glycogen storage in skeletal muscle.
85
How does insulin promote fat storage?
Activates Akt → promotes triacylglycerol (TAG) and FFA storage in adipocytes.
86
How does insulin regulate protein synthesis?
Akt → activates mTORC1 → ↑ protein synthesis, ↓ degradation.
87
What does SREBP1 do under insulin signaling?
Promotes glycolysis and lipogenesis (fat synthesis).
88
What happens to FOXO1 during insulin signaling?
Akt inactivates FOXO1 → ↓ gluconeogenesis (↓ glucose production).
89
What effect does insulin have on glucokinase in hepatocytes?
Increases glucokinase expression via SREBP1c → promotes glycolysis.
90
How does insulin reduce gluconeogenesis in the liver?
By decreasing glucose-6-phosphatase and fructose-1,6-bisphosphatase expression.
91
What enzymes involved in glycolysis are activated by insulin in hepatocytes?
PFK1
Pyruvate Kinase
92
How does insulin promote glycogen synthesis in the liver?
Activates glycogen synthase
Inhibits glycogen phosphorylase.
93
What is insulin’s effect on lipid metabolism in the liver?
Increases triacylglycerol synthesis → glycolysis and lipogenesis.
94
Which tissues express insulin-dependent GLUT4 transporters?
Skeletal muscle
Adipose tissue.
95
What happens to glucose uptake in skeletal muscle when insulin is present?
GLUT4 translocation increases glucose uptake → used for glycolysis or glycogenesis.
96
How does insulin affect amino acid metabolism in skeletal muscle?
↑ AA uptake
↑ protein synthesis
↓ proteolysis.
97
In adipose tissue, what enzyme does insulin upregulate to promote fatty acid uptake?
Lipoprotein lipase (LPL) → breaks down circulating TAGs for storage.
98
How does insulin promote fat storage in adipose tissue?
↑ Lipogenesis and ↓ lipolysis by inhibiting hormone-sensitive lipase (HSL).
99
What happens to glucose metabolism in adipose tissue under insulin influence?
↑ Glycolysis → provides glycerol for TAG synthesis.
100
What are the effects of insulin deficiency on metabolism?
↓ glucose uptake → ↑ fat oxidation, ↑ ketone production → risk of ketoacidosis.
101
What happens to protein metabolism when insulin is present?
↑ Protein synthesis
↓ Proteolysis
↓ Urea cycle activity.
102
What hormone promotes proteolysis during fasting?
Glucagon
Catecholamines.
103
What is insulin’s half-life, and how is it degraded?
~5 minutes; degraded by insulin-degrading enzyme (IDE) or insulinase.
104
What are insulin’s main actions in the LIVER?
↑ Glycolysis
↑ Glycogenesis
↑ Lipogenesis.
↓ Gluconeogenesis
105
What are insulin’s main actions in MUSCLE?
↑ Glucose uptake
↑ Protein synthesis.
106
What are insulin’s main actions in ADIPOSE TISSUE?
↑ Glucose uptake
↑ Lipogenesis
↓ Lipolysis.
107
What does Akt kinase do when activated by insulin?
PROMOTES GLUT4 translocation, glycogen/lipid/protein synthesis
INHIBITS gluconeogenesis and catabolism.
108
Increases blood glucose levels by promoting glycogen breakdown and gluconeogenesis in the liver.
Glucagon
109
What hormone is glucagon's primary counterregulatory partner?
Insulin
110
What is the precursor of glucagon?
Preproglucagon
111
Where is glucagon synthesized?
alpha cells of the pancreatic islets
112
How many amino acids make up glucagon?
29 amino acids
113
Glucagon’s half-life
6 minutes
114
Primary site of glucagon action
Liver
115
Major stimulus for Glucagon secretion
Low blood glucose levels
116
How does insulin affect glucagon secretion?
Inhibits it
117
How does blood flow within the pancreas influence glucagon secretion?
Flows from beta (central) to alpha (peripheral) cells, allowing insulin to suppress glucagon.
118
What receptors stimulate glucagon secretion in response to catecholamines?
β2-adrenergic receptors
119
How do serum amino acids affect glucagon secretion?
Increase glucagon secretion
120
What type of receptor is the glucagon receptor?
Gs protein-coupled receptor (GPCR)
121
What second messenger system does glucagon use?
Activates adenylyl cyclase → ↑ cAMP → activates PKA
122
What transcription factor is activated by glucagon signaling?
CREB (cAMP Response Element-Binding protein)
123
What are the primary actions of glucagon in the liver?
↑ Glycogenolysis
↑ Gluconeogenesis
124
What effect does glucagon have on muscle?
Indirectly increases amino acid release → used for gluconeogenesis
125
What does glucagon stimulate in adipose tissue?
Activates Hormone Sensitive Lipase → ↑ Fatty acid release
126
Source of somatostatin in the pancreas
Delta (δ) cells of the islets of Langerhans
127
Stimulates somatostatin secretion
All types of ingested nutrients and glucagon
128
Inhibits somatostatin secretion
Insulin
129
Inhibits both insulin and glucagon secretion
Somatostatin
130
Function of Somatostatin in Glucose regulation
Modulates/dampens hormone secretion to prevent overshooting glucose control
131
Source of Catecholamines
Adrenal medulla
132
133
What stimulates catecholamine release?
Stress (e.g., fear, trauma, hypoglycemia)
134
What are the metabolic actions of catecholamines?
↑ Glycogenolysis (liver & muscle)
↑ Gluconeogenesis (liver)
↑ Glucagon secretion (via β receptors)
↓ Insulin secretion (via α2 receptors)
135
Overall goal of catecholamines in metabolism
Rapid availability of glucose and fatty acids for energy (fight-or-flight)
136
Where is cortisol produced?
Zona fasciculata of the adrenal cortex
137
What stimulates cortisol release?
Chronic stress via ACTH
138
Metabolic Effects of Cortisol
↑ Gluconeogenesis
↑ Protein catabolism (↑ amino acids)
↑ Lipolysis
↓ Peripheral glucose utilization (insulin antagonism)
139
Goal of cortisol in Metabolism
Long-term energy preservation
Glucose sparing
140
Why does the body have multiple hormones to raise blood glucose but only one to lower it?
Because hypoglycemia is acutely life-threatening, while hyperglycemia is less immediately dangerous — an evolutionary adaptation
141
Hallmark lab finding in diabetes mellitus
Elevated fasting plasma glucose
142
What causes elevated glucose in diabetes mellitus?
Either decreased insulin levels or decreased insulin responsiveness
143
Primary defect in Type 1 Diabetes Mellitus
Pancreatic islets fail to produce insulin
144
Primary defect in Type 2 Diabetes Mellitus
Peripheral tissues are insulin-resistant (even though insulin is present)
145
In Type 1 DM, what happens to insulin secretion?
It is markedly reduced or absent
146
In Type 2 DM, what happens to insulin levels early in the disease?
Often normal or elevated, but ineffective due to resistance
147
Autoimmune destruction of pancreatic β-cells, mediated by T-lymphocytes
Type 1 Diabetes Mellitus
148
Autoantibodies are commonly found in T1DM
Anti-GAD (Glutamic Acid Decarboxylase)
Anti-IA2
Islet Cell Antibodies
149
At what age does T1DM typically present?
Childhood or adolescence (juvenile diabetes)
150
Classic symptoms of T1DM
Polyuria
Polydipsia
Polyphagia
Weight loss, fatigue
151
Are oral hypoglycemic agents effective in T1DM?
No. They are ineffective and contraindicated
152
Metabolic effects result from insulin deficiency in T1DM
↓ Glucose uptake → Hyperglycemia
↑ Lipolysis & β-oxidation → ↑ Ketone production
Muscles rely on fatty acids for energy
153
Life-threatening complication is associated with T1DM
Diabetic Ketoacidosis (DKA)
154
Key features of Diabetic Ketoacidosis (DKA)
↑ Blood glucose
↑ Free fatty acids (FFAs)
↑ Ketones
Requires ICU-level management
155
Most common form of diabetes mellitus
Type 2 Diabetes Mellitus (≈90% of all cases)
156
Major risk factors for T2DM
Visceral obesity
Physical inactivity
157
Insulin resistance in adipose tissue and skeletal muscle
early T2DM
158
How does the pancreas initially compensate for insulin resistance in T2DM?
By producing more insulin → Reactive Hyperinsulinemia
159
What happens after prolonged reactive hyperinsulinemia?
Relative hypoinsulinemia due to beta cell exhaustion
160
What marks the progression of T2DM to a more severe form?
Beta cell failure → inability to produce sufficient insulin
161
What are the cellular-level defects in insulin resistance?
Defective insulin receptor function
Impaired post-receptor signaling
162
Type of adiposity is most closely linked to insulin resistance
Visceral adiposity (central/abdominal obesity)
163
How does lipotoxicity contribute to insulin resistance?
Buildup of triacylglycerols impairs GLUT4-mediated glucose uptake in muscle
164
What cytokine promotes hepatic insulin resistance and impaired lipid metabolism?
TNF-α
165
How does insulin resistance affect hepatic glucose production?
Insulin fails to suppress gluconeogenesis → ↑ hepatic glucose output
166
How do hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) dysfunction contribute to insulin resistance?
Insulin fails to regulate HSL and LPL → Impaired lipid metabolism
167
Name three endocrine conditions associated with insulin resistance.
Cushing’s syndrome (glucocorticoids)
Acromegaly (GH excess)
Pregnancy (gestational diabetes)
168
Ovarian disorder is associated with insulin resistance
Polycystic Ovary Syndrome (PCOS)
169
What genetic/metabolic conditions can cause insulin resistance?
Lipodystrophy
Hemochromatosis
PPARγ mutations
Melanocortin receptor mutations
170
What rare immunologic cause can impair insulin signaling?
Autoantibodies to the insulin receptor
171
Type 1 Diabetes Mellitus (DM)
🟡 Cause: Autoimmune destruction of pancreatic β-cells → No insulin production
🟡 Onset: Usually in childhood or adolescence (sudden onset)
🟡 Body type: Thin or normal weight
🟡 Insulin: Low or absent
🟡 Glucagon: High but can be suppressed by insulin
🟡 Insulin sensitivity: Normal
🟡 Symptoms: Polyuria, polydipsia, polyphagia, weight loss, fatigue
🟡 Treatment: Insulin is required for life
172
Type 2 Diabetes Mellitus (DM)
🟢 Cause: Insulin resistance + eventual β-cell failure
🟢 Onset: Usually in adults >30, but now increasing in youth
🟢 Body type: Visceral obesity (central fat)
🟢 Insulin: Normal to high early; decreases over time
🟢 Glucagon: High and resistant to suppression
🟢 Insulin sensitivity: Reduced
🟢 Symptoms: May be subtle or gradual; often diagnosed late
🟢 Treatment: Lifestyle changes, oral meds (e.g., metformin), insulin if needed
173
Excessive urination due to high glucose levels in urine, which binds to water and causes fluid loss
Polyuria
174
Increased thirst as the body tries to compensate for fluid loss from frequent urination.
Polydipsia
175
Increased hunger because glucose cannot enter the tissues, leading to a sense of starvation
Polyphagia
176
Fasting plasma glucose level for diagnosing diabetes
>126 mg/dL on 2 consecutive days.
177
Diagnostic threshold for the Oral Glucose Tolerance Test (OGTT) in diabetes
2-hour plasma glucose level >200 mg/dL on 2 consecutive days.
178
Diagnostic criterion for non-fasting plasma glucose in diabetes
Symptoms of diabetes + non-fasting plasma glucose >200 mg/dL.
179
HbA1C threshold for diagnosing diabetes
≥6.5% (glycosylated hemoglobin).
180
How does the glucose tolerance curve differ between a normal person and a person with diabetes?
Normal:
Fasting glucose <100 mg/dL, rises to 120-140 mg/dL after glucose ingestion, returns to normal within 2 hours.
Diabetes:
Fasting glucose >110 mg/dL, rises above 200 mg/dL after glucose ingestion, takes longer to return to normal.
181
What happens to the islet cells in diabetes?
Hyalinization occurs, leading to damage and dysfunction of pancreatic islets.
182
Pathophysiology of Type 1 and Type 2 diabetes
Type 1: Beta cells are destroyed, leading to no insulin production.
Type 2: The body becomes insulin resistant.
183
Why is controlling blood glucose important?
Chronic high blood glucose can lead to serious complications, such as Diabetic Ketoacidosis (DKA) in Type 1 diabetes.
184
A serious complication of diabetes, especially Type 1 DM, characterized by hyperglycemia, anion gap metabolic acidosis, and ketonemia.
Diabetic ketoacidosis (DKA)
185
Three key components of DKA
Hyperglycemia
Anion gap metabolic acidosis
Ketonemia.
186
Pathophysiology of DKA
Insulin deficiency prevents glucose use, while glucagon remains unopposed, leading to increased blood glucose, lipolysis, and ketogenesis (ketone production), causing acidosis
187
Common symptoms of DKA
Nausea, vomiting, abdominal pain, lethargy, Kussmaul breathing, acetone breath with fruity odor
188
Signs on physical exam in DKA
Low to normal BP, increased HR and RR, signs of volume depletion (dry skin, low jugular venous pressure), and severe dehydration possibly leading to coma.
189
Treatment for DKA
ICU management with fluid replacement
Insulin administration
Correction of electrolyte imbalances
190
Key blood changes in DKA
Elevated blood glucose (500-900 mg/dL)
High ketones
Anion gap >20 mEq/L
Decreased bicarbonate
pH <7.3
Abnormal lipid metabolism (increased cholesterol)
191
Other causes of metabolic acidosis to differentiate from DKA
Lactic acidosis
Starvation ketosis
Alcoholic ketoacidosis
Uremic acidosis
Toxin ingestion (e.g., salicylates).
192
Microvascular complications of long-standing diabetes
Diabetic retinopathy (blindness)
Diabetic nephropathy (requiring dialysis/transplant)
Diabetic neuropathy (paresthesia, "glove and stocking" pattern, polyneuropathy).
193
Macrovascular complications of long-standing diabetes
Atherosclerosis leading to ischemic stroke, myocardial infarction, and poor circulation, especially in extremities (affecting wound healing in the foot).
194
Treatment for Type 1 Diabetes Mellitus (DM)
Insulin injections, along with diet and exercise
195
Treatment options for Type 2 Diabetes Mellitus (DM)
Diet and exercise
Insulin
Biguanides (e.g., metformin)
Sulfonylureas
Meglitinides
Thiazolidinediones (TZDs)
SGLT2 inhibitors
GLP-1 agonists.
196
Treatment goals for Type 2 DM
HbA1c <7%
Fasting and premeal plasma glucose = 70-130 mg/dL
2-hour postprandial glucose <180 mg/dL.
197
Non-pharmacologic therapies are recommended for Type 2 DM
Dietary modification
Regular isotonic exercise
Weight reduction
Behavior modification
Self-monitoring of blood glucose.
198
Activates AMPK, decreases hepatic insulin resistance, and reduces gluconeogenesis. It does not cause hypoglycemia
Metformin
199
Side effects and precautions of Metformin
Side effects include GI upset and a risk of lactic acidosis
Avoid in renal insufficiency.
200
Activate PPAR-γ to increase peripheral insulin sensitivity and reduce hepatic glucose production. They also lower triglycerides.
Thiazolidinediones (TZDs)
201
Side effects of Thiazolidinediones (TZDs)
Weight gain (fat + fluid) and fluid retention.
202
They act on sulfonylurea receptors to close ATP-sensitive K⁺ channels in β-cells, leading to cell depolarization, Ca²⁺ influx, and increased insulin release.
Sulfonylureas
203
Potential side effect of Sulfonylureas
Hypoglycemia
204
They delay carbohydrate absorption by inhibiting terminal digestion in the intestine.
α-Glucosidase Inhibitors (e.g., Acarbose, Miglitol)
205
Side effects of α-Glucosidase Inhibitors
Flatulence and diarrhea
206
They slow gastric emptying, decrease appetite, and reduce glucagon secretion. Used with insulin.
Amylin Analogues (e.g., Pramlintide)
207
How is Insulin administered, and what are its types?
Insulin is administered subcutaneously
1. Rapid-acting (Lispro, Aspart, Glulisine)
2. Short-acting (Regular insulin)
3. Intermediate (NPH)
4. Long-acting (Glargine, Detemir)
208
Side effects of Insulin
Hypoglycemia
Weight gain.
209
They inhibit the reabsorption of glucose in the kidneys, leading to glucose excretion.
SGLT2 inhibitors
210
Example of a GLP-1 agonist
Semaglutide (Ozempic)
211
Activates the GLP-1 receptor, increasing cAMP, potentiating calcium action, and promoting insulin release
GLP-1 agonist
212
Real-time tracking of glucose via a sensor, with future integration into insulin pumps.
Continuous Glucose Monitoring (CGM)
213
Transplanting insulin-producing beta cells from a donor to restore insulin production.
Beta Cell Transplantation for Type 1 DM
214
Mimics GLP-1, suppressing appetite, delaying gastric emptying, and improving glucose control.
Semaglutide (Ozempic®)
215
Oral glucose triggers greater insulin secretion than IV glucose due to gut hormones like GLP-1 and GIP.
Incretin effect
216
How do GLP-1 and GIP enhance insulin secretion?
Both hormones increase glucose-dependent insulin release from pancreatic β-cells.
217
Stimulate insulin release, suppress glucagon, and slow gastric emptying (e.g., Semaglutide, Liraglutide).
GLP-1 receptor agonists
218
Prolong GLP-1 and GIP activity, enhancing insulin secretion (e.g., Sitagliptin, Saxagliptin).
DPP-4 inhibitors
