DIABETES MELLITUS PART 1 Flashcards
1
Q
What are the major endocrine glands?
A
Pituitary gland, thyroid gland, parathyroid glands, pancreas, adrenal glands, ovaries, and testes.
2
Q
Why are the terms ‘Insulin-Dependent DM’ and ‘Non-Insulin-Dependent DM’ no longer used?
A
Because some Type 2 DM patients use insulin, making the classification based on treatment inaccurate.
3
Q
What does ‘diabetes’ mean in Greek?
A
‘To pass through’ (copious urination).
4
Q
What does ‘mellitus’ mean in Latin?
A
‘Sweetened with honey’ (referring to sugar in urine).
5
Q
What is the most common endocrine disorder?
A
Diabetes Mellitus (DM).
6
Q
What is the difference between Diabetes Mellitus (DM) and Diabetes Insipidus (DI)?
A
Both have polyuria, but DI is due to hypothalamic dysregulation, not glucose metabolism.
7
Q
What is the current classification system for DM based on?
A
Etiology (cause) rather than treatment.
8
Q
What is the phenotype shared by all types of DM?
A
Hyperglycemia.
9
Q
What is the leading cause of morbidity and mortality in DM patients?
A
Cardiovascular disease (CVD).
10
Q
How much higher is the risk of developing CVD in DM patients?
A
3 times higher than non-DM individuals.
11
Q
What are the leading causes of end-stage renal disease, non-traumatic lower extremity amputations, and adult blindness worldwide?
A
Diabetes Mellitus.
12
Q
How has the worldwide prevalence of DM changed from 1985 to 2019?
A
Increased from 30 million to 463 million cases.
13
Q
What factors contribute to the rising prevalence of Type 2 DM?
A
High-caloric diet, increasing obesity, reduced physical activity, and aging population.
14
Q
How many individuals are projected to have diabetes by 2040?
A
642 million.
15
Q
What percentage of individuals with diabetes may be undiagnosed globally?
A
Up to 50%.
16
Q
How does insulin regulate glucose homeostasis?
A
It promotes glucose uptake in peripheral tissues and inhibits hepatic glucose production.
17
Q
What are the major peripheral tissues involved in glucose uptake?
A
Adipose tissue and skeletal muscle.
18
Q
What hormone counteracts insulin?
A
Glucagon, secreted by pancreatic alpha cells.
19
Q
What happens to glucagon levels in DM?
A
Glucagon is increased both fasting and postprandially, stimulating excess glycogenolysis and gluconeogenesis.
20
Q
What is the primary regulator of insulin secretion?
A
Glucose.
21
Q
What happens postprandially to insulin and glucagon levels?
A
Insulin rises, glucagon falls, leading to optimized glucose disposal.
22
Q
Why is insulin called an anabolic hormone?
A
It promotes growth and storage of carbohydrates, fat, and protein synthesis.
23
Q
Which pancreatic cells produce glucagon?
A
Alpha cells.
24
Q
Which pancreatic cells produce insulin?
A
Beta cells.
25
What are the counterregulatory hormones of insulin?
Glucagon, cortisol, growth hormone, catecholamines.
26
What can interfere with insulin function and cause hyperglycemia?
Excess levels of counterregulatory hormones (e.g., cortisol, growth hormone).
27
What is the precursor of insulin?
Preproinsulin.
28
What molecule is co-secreted with insulin and used as a marker of endogenous insulin production?
C-peptide.
29
Why is C-peptide useful in diagnosing T1DM?
It helps determine if the patient has insulin deficiency or complete loss of insulin production.
30
How can C-peptide help distinguish endogenous from exogenous insulin?
Endogenous insulin secretion includes C-peptide, whereas exogenous insulin does not.
31
What is the primary trigger for insulin secretion?
Glucose levels >70 mg/dL.
32
What transporter allows glucose to enter pancreatic beta cells?
GLUT-2.
33
What transporter allows glucose to enter peripheral tissues?
GLUT-4.
34
What is the rate-limiting step in glucose metabolism in beta cells?
Glucose phosphorylation by glucokinase.
35
How do sulfonylureas stimulate insulin secretion?
By closing ATP-sensitive potassium channels, leading to calcium influx and insulin release.
36
What are the two phases of insulin secretion?
A rapid first-phase response and a prolonged second-phase response.
37
What is the primary defect in insulin secretion in both T1DM and T2DM?
Loss of first-phase insulin secretion.
38
What are the main incretin hormones?
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP).
39
What is the function of incretin hormones?
Stimulate insulin secretion, suppress glucagon, and improve glucose regulation.
40
What is the role of GLP-1 receptor agonists in T2DM treatment?
They mimic incretin effects, enhancing insulin secretion and promoting weight loss.
41
How does insulin affect hepatic glucose production?
It suppresses hepatic glucose production and increases glucose uptake.
42
What is the role of GLUT4 in insulin action?
It transports glucose into peripheral tissues, mainly skeletal muscle and adipose tissue.
43
What can activate GLUT4 independently of insulin?
Exercise.
44
What are the metabolic effects of insulin?
Glycogen synthesis, protein synthesis, lipogenesis, and gene regulation in insulin-responsive cells.
45
How was diabetes previously classified?
Based on treatment (Type 1: insulin-dependent, Type 2: non-insulin-dependent).
46
How is diabetes classified now?
Based on the pathogenic process leading to hyperglycemia.
47
What causes Type 1 DM?
Autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency.
48
What are the main characteristics of Type 2 DM?
Insulin resistance, impaired insulin secretion, and increased hepatic glucose production.
49
How does T2DM differ from T1DM in pathogenesis?
T2DM involves insulin resistance and secretory defects, while T1DM results from autoimmune beta-cell destruction.
50
What is the role of beta-cell dysfunction in T2DM?
It contributes to progressive insulin deficiency over time.
51
Why do patients with T2DM have increased hepatic glucose production?
Due to insulin resistance and inappropriate glucagon secretion.
52
What is the primary mechanism of Type 1 Diabetes?
Immune-mediated beta cell destruction leading to absolute insulin deficiency.
53
What are the main defects in Type 2 Diabetes?
Predominantly insulin resistance with relative insulin deficiency or a predominantly insulin secretory defect with insulin resistance.
54
What are monogenic diabetes (MODY) and its genetic causes?
MODY is caused by genetic defects in beta cell development or function, including mutations in HNF-4α, glucokinase, HNF-1α, and others.
55
What is transient neonatal diabetes?
A temporary form of neonatal diabetes that resolves after infancy.
56
What pancreatic diseases can lead to diabetes?
Pancreatitis, pancreatic neoplasia, pancreatic resection, cystic fibrosis, hemochromatosis, and fibrocalculous pancreatopathy.
57
What genetic defects cause insulin resistance leading to diabetes?
Type A insulin resistance, Leprechaunism, Rabson-Mendenhall syndrome, and lipodystrophy syndromes.
58
What endocrinopathies can lead to diabetes?
Acromegaly, Cushing’s syndrome, glucagonoma, pheochromocytoma, hyperthyroidism, somatostatinoma, and aldosteronoma.
59
What drugs or chemicals can induce diabetes?
Glucocorticoids (Prednisone, Dexamethasone), calcineurin and mTOR inhibitors, vacor, pentamidine, nicotinic acid, diazoxide, β-adrenergic agonists, thiazides, and others.
60
What infections can lead to diabetes?
Congenital rubella, cytomegalovirus, and coxsackievirus.
61
What are some uncommon immune-mediated forms of diabetes?
Stiff-person syndrome and anti-insulin receptor antibodies.
62
What genetic syndromes are associated with diabetes?
Wolfram syndrome, Down’s syndrome, Klinefelter’s syndrome, Turner’s syndrome, Friedreich’s ataxia, Huntington’s chorea, and others.
63
What is gestational diabetes mellitus (GDM)?
Diabetes diagnosed during the 2nd or 3rd trimester of pregnancy.
64
What triggers the autoimmune process in Type 1 Diabetes?
Genetic predisposition combined with environmental factors such as viral infections (Coxsackie, Rubella), dietary factors (bovine milk proteins), and vitamin D deficiency.
65
What autoantibodies are associated with Type 1 Diabetes?
Anti-GAD (Glutamic Acid Decarboxylase), Insulin autoantibodies, IA-2/ICA-512, and Zinc transporter 8 (ZnT-8).
66
What is the major susceptibility gene for Type 1 Diabetes?
HLA region on chromosome 6, which encodes Class II MHC molecules involved in immune response.
67
How does insulin resistance develop in Type 2 Diabetes?
Initially, the body compensates with hyperinsulinemia, but over time, beta cells fail, leading to impaired glucose tolerance and eventual diabetes.
68
What are the three core defects in Type 2 Diabetes?
Decreased insulin secretion from beta cells, increased hepatic glucose production, and decreased glucose uptake in muscles and adipose tissue.
69
What role does obesity play in insulin resistance?
Excess adipocytes release adipokines that impair insulin action, especially in central obesity.
70
What is the Ominous Octet in Type 2 Diabetes?
Eight pathophysiologic mechanisms contributing to Type 2 Diabetes, including insulin resistance, beta-cell dysfunction, increased hepatic glucose production, and decreased incretin effect.
71
What is the Egregious Eleven?
An updated model of Type 2 Diabetes pathophysiology including microbiota changes, neurotransmitter dysfunction, and immune dysregulation.
72
How does pancreatic dysfunction contribute to Type 2 Diabetes?
Beta-cell failure leads to decreased insulin secretion, while alpha-cell dysfunction increases glucagon secretion, worsening hyperglycemia.
73
How does hepatic dysfunction contribute to Type 2 Diabetes?
Increased gluconeogenesis and glycogenolysis result in excessive glucose production, leading to fasting hyperglycemia.
74
What is insulin resistance?
A condition in which cells fail to respond effectively to insulin, leading to increased blood glucose levels.
75
How does central obesity contribute to insulin resistance?
Excess abdominal fat releases inflammatory cytokines and adipokines that impair insulin signaling.
76
What is impaired glucose tolerance (IGT)?
A prediabetic state characterized by elevated postprandial glucose due to declining beta-cell function.
77
What is Gestational Diabetes Mellitus (GDM)?
Diabetes diagnosed during the second or third trimester of pregnancy.
78
What percentage of mothers with GDM develop Type 2 DM later?
About 35-45% within the next 10-20 years, with some developing it within 3 years.
79
What is the one-step screening strategy for GDM?
75g OGTT (anhydrous glucose).
80
When should GDM screening be done for high-risk patients?
At the first prenatal visit if the patient has risk factors such as PCOS, obesity, hypertension, dyslipidemia, or a strong family history of DM.
81
When is routine screening for GDM done if no previous DM diagnosis?
At 24-48 weeks AOG using a 75g OGTT.
82
What fasting plasma glucose (FPG) level diagnoses GDM?
≥92 mg/dL (5.1 mmol/L) after 8-12 hours of fasting.
83
What 1-hour plasma glucose (PG) level diagnoses GDM?
≥180 mg/dL (10 mmol/L).
84
What 2-hour plasma glucose (PG) level diagnoses GDM?
≥153 mg/dL (8.5 mmol/L).
85
What is the diagnostic criterion for GDM based on OGTT results?
If one out of the three glucose levels (FPG, 1-hr PG, or 2-hr PG) is above the threshold, GDM is diagnosed.
86
What are the common symptoms of diabetes?
Polyuria, polydipsia, polyphagia, weight loss, fatigue, weakness, blurry vision, frequent infections, slow healing of wounds.
87
Why do patients with diabetes experience weight loss?
Due to protein catabolism from insulin deficiency.
88
Why are frequent infections common in Type 2 DM?
Due to immune dysregulation.
89
What are important aspects of the physical examination in diabetes?
Weight/BMI, retinal examination (fundoscopy), orthostatic hypotension assessment, foot examination, peripheral pulses.
90
What is Acanthosis Nigricans and what does it indicate?
Hyperpigmentation of the nape, knuckles, armpits, axilla, and knees; indicates insulin resistance.
91
What are key clinical features of Type 1 DM?
Lean body habitus, insulin requirement, ketoacidosis propensity, autoimmune disease association.
92
What are key clinical features of Type 2 DM?
Obesity (80%), insulin resistance, hypertension, CVD, dyslipidemia, PCOS.
93
What is Metabolic Syndrome (Insulin Resistance Syndrome)?
A condition where at least 3 of the following are present: obesity, diabetes/pre-diabetes, hypertension, dyslipidemia, PCOS, NAFLD.
94
What is Latent Autoimmune Diabetes in Adults (LADA)?
A form of diabetes with mild autoimmune features occurring in young adults.
95
What is the primary test for diagnosing diabetes in asymptomatic individuals?
HbA1c or Fasting Plasma Glucose (FPG).
96
What are some hindrances in diagnosing diabetes?
A1C variability, lack of standardization in enzyme-linked assays, altered HbA1c in hemoglobinopathies or CKD.
97
What is HbA1c and what does it reflect?
Glycated hemoglobin; reflects glycemic control over the past 3 months.
98
What conditions can alter HbA1c levels?
Hemoglobinopathies, anemia, reticulocytosis, uremia.
99
Who should be screened for diabetes?
Individuals >45 years old every 3 years, overweight individuals with additional risk factors, women with GDM every 3 years.
100
What is the normal fasting plasma glucose (FPG) level?
<5.6 mmol/L (100 mg/dL).
101
What FPG level indicates prediabetes?
5.6-6.9 mmol/L (100-125 mg/dL).
102
What FPG level indicates diabetes?
≥7.0 mmol/L (126 mg/dL).
103
What is the normal HbA1c level?
<5.6%.
104
What HbA1c level indicates prediabetes?
5.7-6.4%.
105
What HbA1c level indicates diabetes?
≥6.5%.
106
What is the normal 2-hour plasma glucose (PG) level in an OGTT?
<7.8 mmol/L (140 mg/dL).
107
What 2-hour PG level indicates prediabetes?
7.8-11.0 mmol/L (140-199 mg/dL).
108
What 2-hour PG level indicates diabetes?
≥11.1 mmol/L (200 mg/dL).
109
What criteria confirm a diagnosis of diabetes?
Symptoms + random PG ≥200 mg/dL, FPG ≥126 mg/dL, HbA1c ≥6.5%, or 2-hr PG ≥200 mg/dL on OGTT.
110
What should be done if a diabetes screening test is abnormal?
Repeat the test on a separate occasion unless there is unequivocal hyperglycemia.
111
What is the earliest abnormal glucose parameter in Type 2 DM?
2-hour PG on OGTT.
112
What is the significance of fasting glucose in diabetes?
It represents hepatic glucose production.
113
How does weight loss affect diabetes management?
It can improve insulin sensitivity and may lead to diabetes remission in some patients.
