metabolism and pancreas Flashcards

1
Q

Respiratory Quotient (RQ)

A

the ratio of the carbon dioxide produced for each oxygen molecule consumed during metabolic process.

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2
Q

When the respiratory quotient is high, carbon dioxide is ____ and oxygen is ____. In order word the oxygen consumption is ____.

A

high
low
high

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3
Q

Basal Metabolic Rate (BMR)

A

clinically measured estimate of the energy used by the body at rest under defined conditions measured as oxygen consumption and expressed in kcal /hour/square meter of body surface area

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4
Q

most of the energy we metabolized is converted to heat with only _____% utilized for actual work

A

25%

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5
Q

pancreatic and other hormones together with CNS help regulate intake and disposition of _____ and retrieve endogenous ____ stores during fasting

A

nutrients

energy

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6
Q

energy is measured in ____

A

calories

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7
Q

what are the 3 basic energy sources?

A

carbohydrates - 4 kcal/g , RQ = 1
fats - 9kcal/g , RQ = .7
proteins - 4kcal/g , RQ = .8

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8
Q

non-shivering thermogenesis

A

energy used to maintain body temperature.

its regulated by the hypothalamus/sympathetic nervous system

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9
Q

diet-induced thermogenesis

A

energy used to digest, absorb, and store nutrients

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10
Q

anabolism

A

synthesis of macromolecules from smaller organic molecules usually requiring energy from ATP

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11
Q

glycogenesis

A

glucose to glycogen ( storage of glucose)

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12
Q

lipogenesis

A

glycerol and fatty acids combined to form triglycerides

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13
Q

protein synthesis

A

protein anabolism

amino acids to protein

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14
Q

catabolism

A

breakdown or degradation of molecules

break bonds and makes ATP

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15
Q

two process of catabolism are:

A

hydrolysis

oxidation

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16
Q

hydrolysis

A

addition of water to break bond

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17
Q

oxidation

A

formation of ATP

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18
Q

glycogenolysis

A

glycogen to glucose (breakdown of stored glycogen)

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19
Q

lipolysis

A

triglycerides broken down to glycerol and fatty acids

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20
Q

proteolysis

A

protein catabolism

proteins broken down to amino acids

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21
Q

glycolysis

A

the lysis or breakdown of glucose to form 2 pyruvate molecules; anaerobic, occurs in cytosol

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22
Q

ketogenesis

A

fatty oxidation in liver that stops at last 4 carbons to form ketone bodies that are released into the blood as alternate energy source for many tissues

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23
Q

glut proteins

A

glucose transport proteins

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24
Q

what are the examples of glucose transport proteins, site of expression, and characteristics?

A
SGLUT1
SGLUT2
GLUT1
GLUT2
GLUT3
GLUT4
GLUT5
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25
Q

Identify the four main hormone producing cells of the pancreatic islets of Langerhans and the hormones they produce.

A

Alpha - glucagon
Beta - insulin
Delta - somatostatin
F (PP) - pancreatic polypeptide

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26
Q

Identify the main physiological factors that regulate insulin release (8)

A
  1. plasma glucose levels ( less than 50 mg/dl= no insulin secreted; greater than 250 mg/dl max is secreted)
  2. gastrointestinal peptide hormones (after meal, it reinforces glucose to increase insulin)
  3. amino acids (increase pancreatic insulin release)
  4. parasympathetic nervous system
  5. sympathetic nervous system (beta 2 increases insulin release, and alpha 2 adrenergic receptors decrease insulin release)
  6. stress (Epi is released and a decrease in insulin occurs)
  7. glucagon (increases insulin release)
  8. exercise (decreases insulin release)
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27
Q

insulin release is stimulated by which factors? (9)

A
hyperglycemia
amino acids
K+
FFA/ketoacids
GIP - gastric inhibitory peptide
GLP1 - glucagon like peptide 1
glucagon
parasympathetic innervation (Ach Muscarinic receptor)
sulfonylurea
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28
Q

insulin release is inhibited by which factors? (6)

A
hypoglycemia
somatostatin
exercise
leptin
sympathetic innervtion
diazoxide drugs
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29
Q

Identify the major physiological actions of insulin (11)

A
  1. increase glycogenesis
  2. increase cellular uptake of glucose, amino acids, K+, phosphate, magnesium
  3. increase cellular glucose use (glycolysis)
  4. increase adipose tissue conversion of glucose to alpha glycerophosphate
  5. increase storage of fat in adipose tissue (lipogenesis)
  6. decrease production of ketone bodies (antiketogenic)
  7. decrease plasma levels of FFA and ketones
  8. decrease plasma amino acid levels
  9. suppression of appetite
  10. growth and development
  11. stimulation of sodium/K+ ATPase
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30
Q

insulin increases the following:

A

glucogenesis
protein synthesis
lipogenesis
glycolysis

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31
Q

insulin decreases the following:

A

glycogenolysis
protein degradation
lipolysis
gluconeogenesis

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32
Q

Identify the major physiological actions of somatostatin, and the clinical applications of this peptide.

A
  • inhibition of insulin and glucagon secretion
  • decreases GI motility, secretion, blood flow
  • inhibition of release of pituitary hormones
  • synthetic analogs used clinically to visualize and inhibit secretions of endocrine function
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33
Q

Identify the main physiological factors that regulate glucagon release. (4)

A
  • influenced by decrease in plasma glucose levels
  • fasting increases release
  • ANS increase release bc of muscarinic receptors (parasympathetic)
  • sympathetic increases release via beta2 receptors
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34
Q

what factors stimulate glucagon release (7)

A
hypoglycemia
amino acids
stress
exersice
GI hormones (CCK, GIP, gastrin)
parasympathetic 
sympathetic (beta2)
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35
Q

glucagon release is inhibited by what factors?

A
hyperglycemia
carbohydrates
free fatty acids
ketoacids
insulin
somatostatin
GI hormones (GLP1 and secretin)
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36
Q

Identify the major physiological actions of glucagon. (12)

A
increases:
glycogenolysis
gluconeogenesis
protein degradation
lipolysis
ketogenesis
plasma glucose levels
FFA and ketoacid plasma levels
Decreases: 
glycogenesis
protein synthesis
lipogenesis
glycolysis
plasma amino acid levels
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37
Q

Compare and contrast the insulin receptor and the glucagon receptor.

A

similarities:

  • made by pancreatic cell
  • inhibit somatostatin
  • stimulate amino acids
  • both are peptides

differences:

  • glucagon made by alpha pancreatic cell
  • insulin made by beta pancreatic cell
  • reverse roles in catabolic and anabolic reactions
  • what stimulates one, inhibits the other
  • insulin increases use of glucose as energy source and increases storage of excess glucose
  • glucagon stimulates glucose output by the liver and mobilizes energy stores and maintains plasma glucose levels between meals
  • insulin activates transmembrane tyrosine kinase receptors
  • glucagon receptors act through G-protein to stimulate adenylyl cyclase and increase cAMP
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38
Q

Identify the endocrine physiology regulating plasma glucose levels.

A

when glucose is high insulin is secreted. this stimulates the increased uptake of glucose. the excess glucose is converted to glycogen and stored or its converted to fat and stored in adipose tissue. the result is a decrease in blood glucose.
when blood glucose levels are low, theres a decrease in insulin secretion which causes a decrease in uptake of glucose by tissues. glycogen is broken down to glucose in the liver which release glucose in the blood. the glucose is synthesized from amino acids by the liver which releases glucose to the blood as well.
hypoglycemia (fasting) increases glucagon release as do exercise and stress
hyperglycemia decreases glucagon release
decrease in plasma FFA levels increase glucagon release
parasympathetic decreases glucagon release and increases insulin release
(muscarinic)
sympathetic decreases glucagon release and increases insulin release (beta2)
plasma glucose 250mg/dl insulin is secreted

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39
Q

Identify how the regulation of key metabolic enzymes produces the physiological responses to insulin and the glycemic hormones.

A

-glucose is taken up by pancreatic beta cells by GLUT2 and is converted to G6P by hexokinase. glucose is metabolized by beta cells to produce ATP. In beta cells, the ATP/ADP ratio is proportional to the extracellular plasma glucose level.
-gastrointestinal hormones, released after a meal, reinforce effects of glucose, increasing insulin release. GI hormones include gastrin, secretin, CCK, GLP1
after a meal, the ratio of insulin to glucagon rises by 10 due to increased insulin. this increases cellular glucose uptake and use, glycogenesis, increased adipose tissue lipoprotein lipase activity, FFA uptake and lipogenesis, increased amino acid uptake and protein synthesis
Glucagon increases activity of gluconeogenic enzymes: G6phosphatase - allows liver to export glucose, fructose1,6-bisphosphatase, phosphoenolpyruvate caboxykinase.
glucagon increases hepatic glycogenolysis by increasing activity of glycogen phosphorylase

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40
Q

Compare and contrast the pathophysiological events resulting in type 1 and type 2 diabetes mellitus.

A

type 1 DM:
low or no plasma insulin level
destruction or malfunction of beta cells and often caused by autoimmune process
type 2 DM:
insulin resistance or insulin secretion defect; reduced sensitivity to insulin
plasma insulin levels are often normal or may even by elevated early in progressions. patients often have low plasma insulin levels later in the progression of the disease

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41
Q

Identify gestational diabetes mellitus

A

found in pregnant women who have never had diabetes but have hyperglycemia during pregnancy
hormones from placenta decrease the action of mother’s insulin
insulin resistance makes it hard for mother’s body to use insulin and up to 3 times as much insulin may be required for response
affects mother in late pregnancy
if untreated can cause baby’s pancreas to make extra insulin to get rid of blood glucose

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42
Q

symptoms of diabetes mellitus 1 and 2

A
hyperglycemia
polyuria
polydipsia
polyphagia
dehydration
weight loss (type 1)
obesity (type 2)
hyperlipedemia
ketoacidosis
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43
Q

long term effects of diabetes mellitus

A

retinopathies
angiopathies
neuropathies
nephropathies

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44
Q

beta cell tumors

A

low fasting glucose <50 mg/dl
weight gain
sympathetic NS response to hypoglycemia:
-palpitations, sweating, tremors, hunger, anxiety
CNS:
-bizarre behavior, convulsions, coma
diagnosis: elevated fasting insulin and C peptide
treatment: remove tumor
- inhibit insulin secretion (diazoxide)

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45
Q

alpha cell tumors

A

tumor in pancreas causehyperglecemia

symptoms are like diabetes, however insulin should counter balance alpha tumors

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46
Q

what are the hormones of the pancreas

A

glucagon - alpha cells
insulin - beta cells
somatostatin - delta cells
pancreatic polypeptide - F cells

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47
Q

what cells are stimulated in high glucose

A

beta cells - insulin breaks down glucose

48
Q

when K+ channels are opened, what happens to insulin?

A

inhibited - efflux of K+ causing membrane hyperpolarization

49
Q

T/F a depolarized membrane secretes insulin

A

true - increasing ATP causes depolarization. Ca influx also stimulate insulin secretion

50
Q

what natural compound increases the stimulation of insulin release

A

incretins - byetta pen injections is the synthetic drug made

51
Q

what stimulates insulin secretion

A
sulfonylurea drugs (close K channels)
hyperglycemia
glucagon
GLP1
GIP
parasympathetic
52
Q

what inhibits insulin secretions

A

diazoxide drugs (open K channels)
hypoglycemia
somatostatin
sympathetic innervations

53
Q

glucose movement into cells is increased by insulin through which transport?

A

GLUT4 - increases the uptake of glucose into the cell

54
Q

what breaks downs GLP1?

A

DPP4 _ drugs are used to target this enzyme to keep GLP1 around longer for type 2 diabetes

55
Q

what increases the level of glucose in the body?

A

glucagon - opposite effect of insulin stimulation and inhibition

56
Q

glycolysis, lypogenesis, protein synthesis, and glycogenesis are stimulated by?

A

insulin

57
Q

ketogenesis, gluconeogenesis, lipolysis, protein degradation, and glycogenolysis are stimulated by?

A

glucagon

58
Q

diabetes mellitus is the lack of what?

A

insulin type1- insulin dependent (destruction of beta cells)

type 2 - non-insulin dependent (reduced sensitivity to insulin)

59
Q

diabetes insipidus is the lack of?

A

ADH

60
Q

normal fasting glucose is?

A

less than 100 mg/dl

61
Q

diabetes mellitus is classified at what glucose levels?

A

greater then 126 mg/dl

62
Q

what type of diets affect pregnant women?

A

gestational diabetes - insulin resistance may be produced or exacerbated by placental hormones

63
Q

someone with hypoglycemia and increased C-peptide levels have?

A

beta cell secreting tumor (insulin overdose would have low levels of c-peptide)

64
Q

SGLUT1 site of expression

A
S3 segment of proximal kidney tubules
intestinal mucosa (apical membrane)
65
Q

SGLUT2 site of expression

A

S1 and S2 segments of proximal tubules (apical membrane)

66
Q

GLUT1 site of expression

A
S2 and S3 proximal tubule basal
brain
RBC
endothelium
most other tissue
67
Q

GLUT2 site of expression

A

S1 proximal tubule basal
liver
pancreatic beta cells
intestine basal

68
Q

GLUT3 site of expression

A

brain
placenta
testes

69
Q

GLUT4 site of expression

A

skeletal
cardiac muscle
fat cells

70
Q

GLUT 5 site of expression

A

small intestine

sperm

71
Q

SGLUT1 characteristics

A

cotransports 1 glucose and 2 Na

72
Q

SGLUT2 characteristics

A

cotransports 1 glucose and 1 Na

73
Q

GLUT1 characteristics

A

high affinity for glucose (not fructose)

74
Q

GLUT2 characteristics

A

functions as glucose sensor in pancreatic beta cells

glucose entry into liver cells and beta cells are normally proportional to the glucose level in the blood

75
Q

GLUT3 characteristics

A

primary glucose transporter in neurons

76
Q

GLUT4 characteristics

A
  • high affinity insulin-responsive glucose transporter
  • up-regulated by insulin
  • insulin causes insertion of GLUT4 into muscle cell plasma membrane, also activates glut4 gene so that more transporter proteins are synthesized, increasing capacity for glucose transport into muscle and adipocytes
77
Q

GLUT5 characteristics

A

transports fructose

78
Q

Anabolic reactions are usually stimulated by ___

Anabolic reactions are usually inhibited by ___

A

insulin

glucagon

79
Q

Glucose metabolism is stimulated by ___

Glucose metabolism is inhibited by ___

A

insulin

glucagon

80
Q

Anabolic reactions

A

Glycogenesis
Lipogenesis
Protein synthesis

81
Q

Catabolic reactions

A

Glycogenolysis
Lipolysis
Proteolysis

82
Q

Gluconeogenesis is stimulated by

A

glucagon, epinephrine, GH, and *cortisol

83
Q

Gluconeogenesis is inhibited by

A

insulin

84
Q

Glucagon-Like Peptide-1 (GLP-1)

A

incretin activity = ↑ insulin; ↓ glucagon; satiety activity

85
Q

Ghrelin

A

Stimulates gastric activity, GH & appetite

86
Q

A genetic defect in ____ causes maturity-onset diabetes of the young (MODY) a rare form of type 2 diabetes mellitus

A

glucokinase

87
Q

oral hypoglycemic drugs

A

Sulfonylureas

88
Q

Second generation sulfonylureas

A

Glyburide
Glipizide
Glimepride

89
Q

First generation sulfonylureas

A

Chlorpropamide
Tolazamide
Acetohexamide
Tolbutamide

90
Q

Incretins (GIP & GLP-1) stimulate ____ secretion

A

insulin

91
Q

Only three of the twenty amino acids found in our food lead to secretion of insulin. What are they

A

glycine, alanine, arginine

92
Q

the strongest insulin secretagogue is

A

arginine

93
Q

Insulin release is stimulated by:

A
Hyperglycemia
amino acids, K+, FFA\ketoacids
Glucagon-like peptide (GLP-1)
Glucagon
Gastric inhibitory peptide (GIP)
Sulfonylurea drugs
Parasympathetic innervation
94
Q

Insulin release is inhibited by:

A
Hypoglycemia
somatostatin
exercise
leptin
insulin
diazoxide drugs 
sympathetic innervation
95
Q

Anabolic reactions and Catabolic reactions:

insulin actions

A
anabolic:
increases glycogenesis 
increases protein synthesis
increases lipogenesis
catabolic:
increases glycolysis
decreases glycogenolysis
decreases protein degradation
decreases lipolysis
decreases gluconeogenesis
decreases ketogenesis
96
Q

During fasting conditions, several hormones act to ensure that the brain is supplied with glucose

A

Glucagon
Ephinephrine
Cortisol
Growth hormone

97
Q

Inhibit the enzyme that breaks down the incretins GLP-1 & GIP

A

DPP-4 inhibitors; enhances incretin actions

98
Q

DPP4 inhibitor enhances incretin actions resulting in

A

increase insulin
decrease glucagon
decrease apetite

99
Q

examples of DPP-4 inhibitors

A

Sitagliptin (januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Vildagliptin (Galvus)

100
Q

Glucagon Release Stimulated by

A
Hypoglycemia
Amino acids 
Stress & exercise
GI hormones CCK, GIP, gastrin
Parasympathetic innervation
Sympathetic innervation
101
Q

Glucagon Release Inhibited by

A
Hyperglycemia
Carbohydrates
Free fatty acids & ketoacids
Insulin
Somatostatin
GI hormones GLP-1 & secretin
102
Q

coupled to G proteins that stimulate adenylate cyclase

A

Glucagon

103
Q

Anabolic reactions and Catabolic reactions:

glucagon action

A

Anabolic reactions:
Glycogenesis- decrease
Protein synthesis- decreases
Lipogenesis- decreases

Catabolic reactions:
Glycolysis - decreases
Glycogenolysis- increases
Protein degradation- increases
Lipolysis- increases
Gluconeogenesis - increases
Ketogenesis- increases
104
Q

increases glycogen breakdown, glucose formation, amino acid metabolism and ketone formation by the liver
increases the breakdown of fat

A

glucagon

105
Q

Insulin stimulates a __ that removes phosphate from the enzyme

A

phosphatase

106
Q

Glucagon stimulates ____ which phosphorylates the same enzyme

A

protein kinase A

107
Q

F6P to F2P6P is accomplished with ___.

the inverse is accomplished by ____

A

insulin

glucagon

108
Q

____ stimulates facilitated diffusion out of hepatocytes:
Glucose 6-phosphatase: Glucose 6-phosphate converted to glucose
Concentration gradient favors glucose exiting the cell via ___

A

Glucagon

Glut-2

109
Q
Diabetes Mellitus Type 2
Insulin Secretion
Onset
% diabetes
Defect
Obesity 
Ketosis
Treatment
A

Non-insulin-dependent

insulin secretion: increase, Normal or decrease
onset: Adulthood, Slow
% diabetes: ~95%
Defect: Reduced sensitivity to insulin 
Obesity: Yes 
Ketosis: Rare
Treatment: Dietary control & weight reduction; 
oral hypoglycemic drugs, Insulin
110
Q

Diabetes Mellitus Type 1

Insulin Secretion
Onset
% diabetes
Defect
Obesity 
Ketosis
Treatment
A

Insulin-dependent
(lack insulin)

insulin secretion: Little or none
onset: Childhood Rapid
% diabetes: ~5%
Defect: Destruction of beta cells
Obesity: No
Ketosis: Common
Treatment: Insulin injections; dietary management
111
Q

Acanthosis Nigricans

A

Benign form commonly caused by elevated insulin levels stimulating abnormal growth of skin

112
Q

Types of Acanthosis Nigricans

A

Benign:
Insulin resistance/obesity related (IRORAN)
Medication induced
Hereditary benign

Malignant:
Cancer
Glandular disorders

113
Q

Diabetes Mellitus : Long term effects of hyperglycemia

A

Retinopathies - major cause of blindness

Angiopathies - poor circulation, ulcerations, amputations

Neuropathies - loss of feeling, tingling sensations

Nephropathies - kidney damage & renal failure

Non-retinal visual problems - lens distortion and cataracts

114
Q

Biguanides

A

a plant known for several centuries to reduce some symptoms of diabetes mellitus

115
Q

the most commonly prescribed oral DM medication

A

Metformin

116
Q

Drugs used to treat Type-2 Diabetes Mellitus

A
Oral
Biguanides: Metformin
Sulfonylureas: Gliburide, Glipizide
Meglitinides: Nateglinide, Repaglinide
Alpha-glucosidase inhibitors: Acarbose, Miglitol
Thiazolidinediones: Rosiglitazone
Dipeptidyl peptidase 4 (DPP-4) inhibitors: Sitagliptin, Saxagliptin, Vildagliptin 
Injection
Insulin
Incretin mimetics
Amylin analogs
117
Q

Macrosomia (“fat baby“) risks

A
risk of damage to shoulders during birth
risk for breathing problems
may have very low blood glucose levels at birth 
high risk for obesity
type 2 diabetes later in life