Diabetes, Peripheral Neuropathy and Metabolic Syndrome Flashcards
Polyuria
Excessive urination
Polydipsia
Excessive thirst
Nocturia
Urination at night
What does diminished foot arterial pulse indicate?
Possible peripheral vascular disease
Why might you order a fasting blood glucose?
If you have a peripheral neuropathy, high BMI we need to exclude diabetes.
How do we diagnose diabetes on one visit?
Patient presents with ketoacidosis, hyperglycemia, plasma glucose of >200mg/dl
What is the reference interval for glucose?
60-99mg/dl
What if we don’t have all the symptoms of diabetes we can only diagnose when?
On two separate visits when glucose is >126 fasting, >200 OGTT, >6.5 A1c
HHS?
More likely in DMT2, poorly controlled, hyperglycemia and hyperosmolality.
Why do T2DM patient not usually experience ketoacidosis?
Even thought they are insulin resistant they produce enough to avoid ketosis.
OGTT?
Measure fasting plasma glucose, administer glucose, measure 2 hours later.
What amount of glucose should we use in children and adults for OGTT
75mg for adults, weight dependent in children
A1c?
A glucose that is added nonenzymatically to hemoglobin - this is glycated hemoglobin. High A1c >6.5 indicates diabetes.
Hemoglobin A1c is an indicator of systemic glycation. What are the physiological effects?
When the retina leaks protein it can cause blindness. When in the kidney it is a marker of kidney failure.
With only hyperglycemia on one occasion we can’t diagnose diabetes. How many visits does it take?
2 visits with hyperglycemia can lead to a diagnosis of?
What defines elevated glucose but not hyperglycemia?
Impaired fasting glucose
What are borderline measurements for predicting increased risk of diabetes?
IFG, IGT, A1c predict increased risk.
What is IFG, IGT and borderline A1c called?
prediabetes (not diagnosis but description)
IFG
Impaired Fasting Glucose
IGT
Impaired Glucose Tolerance
What is indicated in pre diabetes?
More frequent visits, diet, exercise can reduce risk by 60%
What are symptoms for DMT2?
Middle aged, obese, minority, mild hyperglycemia, no ketosis
If a patient presented with complications of diabetes should we test further?
Yes, A1c, OGTT, IFG
What percentage of DMT2 patients present with complications?
15%
Macrovascular disease (what three vessels)?
Coronary artery, Carotid artery, peripheral arteries.
Microvascular disease (what are the manifestations) ?
Kidney and eye problems. Neuropathy.
Neuropothy (What are the manifestations)?
Peripheral = loss of sensation, glove and sock sensation. Debilitation pain, loss of position sense. Mononeuropathy = Cranial nerve infarction. Autnomic = GUT problems leading to diarrhea, impotence.
TIA?
Transient ischemic attack (thrombosis that doesn’t lead to stroke)
Claudication?
Pain, fatigue and tiredness in the extremities.
Postural hypertension?
Dizziness upon standing - this is due to neuropathy in the autonomic nervous system
What are the causes of complications in diabetes?
CVD, retinopathy, nephropathy, neuropathy
What are the risk factors of diabetes?
Male, age, hyperlipidemia, hypertension, smoking, obesity
What does hyperglycemia cause?
Retinopathy, Nephropathy, Neuropathy
What factors other than hyperglycemia cause nephropathy?
Hypertension, familiar diabetic neuropathy, hyperlipidemia
Why does pregnancy increase risks?
Growth factors increase vascular growth, increased need for C-Section, increased hypertension and pre-eclampsia
What the increased risk for unborn babies when the mother has diabetes?
Congenital malformations Fetal Death Inutero Premature birth NICU Hypercalcemia Hyperbilirubinemia DMT2 in adulthood LGA - large for gestation age.
In the first trimester hyperglycemia is a?
Teratogen
Dystocia
pelvic / cephalo disproportionality
What is the most common cause of death in DMT1?
CVD and Renal failure (renal failure has longer to develop)
What is the most common cause of death in DMT2?
CVD
What are common secondary causes of hypertension?
< 5% of hypertension causes Renal failure, hyperaldosterone
Nephrothapy can be caused by?
Diabetes and hypertension
What is small amounts of albumin in the urine an early sign of?
Glomerular and endothelial disfunction. THis is a way of evaluating the kidney in someone with diabetes.
What is the source of energy in the shortterm in muscle?
Creatine phosphate even before or along with ATP
How do we test for CVD in a person with diabetes?
Lipid panel
How do we prevent the complication of diabetes?
Good glycemic control. It decreases complications by 50%
Etiology of DMT2
–> Insulin resistance –>Obesity
How does insulin resistance cause hypertension?
Na+ Retention
Vasoconstriction (sympathetic tone)
Hypertrophy of vascularity (insulin as growth factor)
Increased Na/K ATPase pump
What are the consequences of hyperinsulinism? DMT2
Atherosclerosis Hypertension Hypercoagulability Hyperandrogenism Hyperuricemia (GOUT) Acanthosis Nigricans
The consequences of inadequate insulinization?
Dysglycemia
Dyslipidemia
Nonalcoholic liver disease
hyperinsulinism –> insulin resistance =
metabolic syndrome
What is metabolic syndrome known as?
Insulin resistance syndrome
Dysmetabolic Syndrome X
What are the characteristics of central obesity?
increased circumference
Waste to hip ration
Subcutaneous and visceral fat distribution
What fat has the greatest effect on insulin resistance?
Visceral fat (hence liposuction doesn’t help)
Why is visceral fat more of an impact on insulin resistance?
It drains directly into portal drainage and into the liver.
How does obesity cause insulin resistance?
(1) Increased FFA deposition in liver, muscle and beta cell causes insulin resistance.
(2) Fat throughout the muscle causes increased TNF-alpha and insulin resistance in muscle.
(3) Cortisol increase can cause obesity.
ApoB + Insulin =
risk increases 11x
High ApoB =
High LDL
Increased glucose –>?
(1) Increased inflammation –> fibrinogen –> Fibrin –> Procoagulant
(2) Adipose cells release plasminogen-activator inhibitor
(3) When tissues are injured they release tissue plasminogen activator which is responsible for forming plasmin which breaks down fibrin and break up thrombins.
(4) if we deactivate PAI we turn off the breakdown of clots.
Hyperandrogenism pathogenesis?
insulin resistance –> hyperinsulinism –> FSH –>LH –> Androgens
What are the consequences of Hyperandrogenism?
Hirsutism
Polycystic ovary
Dyslipidemia (high amount of lipids in blood)
Hypertension
Hyperuricemia (GOUT)
Hyperinsulemia –> Increased PCT reabsorbtion of Na+ and decreased uric acid secretion.
Acanthosis Nigricans?
Thickening, darkening and benign skin in folds
What are the consequences of inadequate insulination (not enough insulin action)
Dysglycemia
Dyslipidemia
Nonalcoholic liver disease
What kind of dyslipidemia is seen in MS
Low HDL
Dense LDL
Increased TAG and VLDL
Increased ApoB –> Increased VLDL –>Dense LDL
What does a macrophage grab ApoB lipoprotein?
It binds to the LD receptor
What is non-alcoholic liver disease?
Increased FFA delivery to liver
This is due to higher quantities of lipid in the blood.
What percentage of adults have MS?
25% (and 4% of adolescents)
What is the underlying pathophysiology of DMT2?
(1) Insulin concentration (2) Tissue sensitivity to insulin. Initial lesion = Insuline resistance, Later lesion = Reduced insulin secretion.
Chronic hyperglycemia does what to beta cells?
It damages them and reduces insulin secretion.
What are the best nonpharmacological ways to manage DMT2?
exercise, reduced sugar and carbs in diet, weight loss
What drugs stimulate endogenous insulin production?
sulfonylureas, Meglitinidines,
What drugs stimulate Incretin production?
Exenatide
What drugs reduces DPP-4?
Sitagliptin, Linagliptin
What does reduction of DPP-4 do?
It inhibits the breakdown of incretin so continued improved insulin release.
What are the endogenous incretins?
Glucagon-like Peptide (GLP) and Gastric inhibitory polypeptide (GIP)
Can insulin be used in treatment of DMT2
Remember [insulin] X tissue sensitivity
What do thiazolidinediones do?
They bind to nuclear receptors and increases insulin resistance by inhibiting transcription of a gene that decreases insulin resistance.
How does metformin work?
Reduces hepatic output of glucose
How does amylin work?
Reduces / slows gastric emptying
What are the sources of amino acids?
Dietary proteins and endogenous (within cells) protein turnover.
How do we get nonessential AA’s
Via De Novo AA synthesis
What are non-protein AA derivatives?
Neurotransmitters etc.
What are the essential AA’s (ones we must eat)
PVT TIM HiLL
What are conditionally essential AA’s?
They are AA’s we can make if we have enough of the essential AA precursors
What enzyme breaks proteins in the stomach?
Pepsin
What enzymes break proteins in the intestinal lumen?
Trypsin and Chymotrypsin
What does carboxypeptidase do?
Breaks peptides into AA’s
How do we get AA’s into the cell?
Via a Na+ dependent transporter that is a symporter (secondary active transporter).
How is the Na+ Dependent transport powered?
By the Na+ / K+ gradient created by the Na+ / K+ ATPAse pump.
What is excreted in excess when Gout is present?
Uric Acid
What are the two pathways for degrading proteins?
(1) Acid degradation of protein in lysosome or phagolysosomes
(2) Ubiquitin dependent pathways via proteosomes
What are the two nitrogen balances we need to consider?
(1) Positive and (2) negative
Why do we need positive negative balance?
For growing children
Pregnancy
Wound Healing
Recovering adult
What are the results of negative balance?
Starvation
Malnutrition
Disease
What type of AA’s must be consumed?
Essential AA’s - the can’t be made de novo
What does AA’s in urine mean?
It is a sign of illness
What is the chief purpose of the urea cycle?
To remove excess nitrogen and formation of arginine.
What is the purpose of transamination?
It is a way to transfer of alpha-amino groups from amino acids to form alpha-keto acids and vice versa. This is a way to form one AA from another.
What four amino acids are not transaminated?
Proline, hydroxyproline, lysine, threonine
What happens with a deficiency of B6 vitamins?
You impair transamination and also the production of neurotransmitters.
How is GDH regulated?
Via allosteric control by ATP and ADP
How does ATP regulate GDH?
Reduces rate of AA oxidation
How does ADP regulate GDH?
Stimulates: and glutamate synthesis is increased
How does D-Amino Acid Oxidase protect against bacteria?
Bacteria requires D-AA for cell walls.
