| What are the symptoms of hypoglycemia? | Feeling shaky, anxiousness, sweat, chills, irritability, confusion, tachycardia, feeling lightheaded, hunger, nausea, pallor, sleepiness, blurred vision, numbness of lips, headaches, nightmares during sleep, seizures and sometimes cardiac arrest |
| What is the whipple triad of hypoglycemia? | symptoms of hypoglycemia, Documentation of low glucose levels (<50), and relief of symptoms following ingestion of glucose. |
| What are the main causes of hypoglycemia in adult non-`diabetic patients? | Drugs (insulin or insulin secretagogue, alcohol..)
Critical illnesses (hepatic, renal or cardiac failure, sepsis (in ICU seen), inanition (hunger).
Hormone deficiency (cortisol, glucagon and epinephrine- for insulin deficient DM pt)
Nonislet cell tumor (IGF-II producing tumor)
Endogenous hyperinsulinism
Accidental, surreptitious, or malicious (admin of insulin) |
| What are the endogenous causes of hyperinsulinism? | Insulinoma
Functional beta cell disorder (nesidioblastosis- hypertrophy of beta cells in pancreas due to obesity)
noninsulinoma pancreatogenous hypoglycemia (physiologic insulinoma)
Post-gastric bypass hypoglycemia (due to high amount of insulin according to high weight and increased incretin (GLP-1) levels
Insulin auto-immune hypoglycemia (causing accumulation and complexation of insulin increasing half-life)
antibody to insulin/ insulin receptor.
Insulin secretogogue (sulfarurease, amaril... stimulating beta cells) |
| What is the physiology of insulin? | It is first produced as proinsulin in beta cells, which is made of insulin + Connective (C) peptide.
It goes to cells where it acts on multiple receptors to increase glycogen synthesis, fat synthesis, protein synthesis
Antagonist is glucagon (increasing gluconeogenesis and glycogenolysis) |
| What is the role of epinephrine in glycemia? | increases hepatic glucose production stimulating glycogenesis and gluconeogenesis.
Inhibits glucose disposal by insulin-dependent tissues. |
| What is the role of cortisol in glycemia? | They act on many levels in order to increase glucose in blood, this includes stimulating glucagon, inhibiting insulin (pancreas)
Impaired incretin effect (intestine)
increased glucose production (liver)
increased lipolysis (adipose)
decreased muscle mass and increased proteolysis (muscles)
capillary recruitment decreased |
| What is the role of GH in glycemia? | GH stimulates liver to produce IGF
IGF-1 increases insulin sensitivity, GH stimulates gluconeogenesis, lipolysis causing hyperglycemia, but also causes increased insulin resistance, resulting in hyperinsulinemia.
But in acromegaly pt, IGF1 isn't able to overcome insulin-resistant state by GH. |
| What is the effect of fasting on glucose? | There are 4 levels of fasting:
Fed (within 4 hours of eating, used glucose is exogenous)
Fasted (4-12 hours after eating, liver stimulate glycogenolysis)
Early starved (12 hours - 16 days, gluconeogenesis starts)
Late starved (after 16 days, only gluconeogenesis and glycogenolysis done) |
| How is the production of ketone bodies during fasting? | We usually screen beta-hydroxy buteric acid level
It is seen to increase with starvation, ketogenic diet, ketosis in exercise. |
| How is the diagnostic evaluation of hypoglycemia? | Whenever we have a pt with syncope/ pre-syncope, first thing to do is obtain blood glucose concentration, if it is low (<55) draw blood for glucose, insulin, C-peptide, and oral hypoglycemic agent.
If it is symptomatic, we shouldn't delay the treatment of the etiology.
If we can't undergo these, go for 72-hour fasting test. |
| What is the 72-hour fast test? | Pt is allowed to drink non-caloric drink and given IV hydration, glucose checked every 6 hours, if it goes below 55 at any time, get C-peptide, proinsulin, insulin, beta hydroxybuteric acid, and oral hypoglycemia screen.
then after 72 hours, give glucagon, if hypoglycemia is caused by insulin, when given glucagon glucose should increase by >25 mg/dl
In normal individual (they have asymptomatic hypoglycemia, hormonally mediated glucose regulation, gluconeogenesis 50% of glucose production after overnight fasting, and almost all glucose after 42 hours, any hypoglycemia would occur only if there is a defect in ability to maintain normoglycemia. |
| What are the test endpoints of 72-hour fasting test? | when glucose <45, symptoms or signs of hypoglycemia occur, end of 72 hours or when glucose <55 with other 2 whipple triad seen before. |
| What are the causes of hypoglycemia related to insulin excess? | Insulinoma, insulin injection (factitious hypoglycemia), insulin secratagogue, reactive hypoglycemia, post-bariatric surgery hypoglycemia |
| What are the lab findings for an exogenous insulin dose causing hypoglycemia? | Glucose (<55)
Insulin (>>3)
C-peptide (<0.2)
Proinsulin (<5)
Beta-hydroxy (<2.7)
Glucose increase after glucagon (>25)
Circulating oral hypoglycemic agent (-)
antibody (-) |
| What is post-pradial hypoglycemia? | AKA reactive hypoglycemia, caused by excess secretion of insulin after eating a sugary meal (within 5 hours of eating got symptoms)
Causes include (Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), post-bypass, autoimmune, idiopathic)
Tested by mixed-meal diagnostic test, screened for 5 hours, every 30 min get blood samples for tests (same as others)
interpretation similar to 72-hour fasting test |
| What are the lab findings for insulinoma, NIPHS, PGBH (post gastric by pass)? | Glucose (<55)
Insulin (>>3)
C-peptide (>0.2)
Proinsulin (>5)
Beta-hydroxy (<2.7)
Glucose increase after glucagon (>25)
Circulating oral hypoglycemic agent (-)
antibody (-) |
| What are the lab findings with oral hypoglycemia agent ? | Glucose (<55)
Insulin (>3)
C-peptide (>0.2)
Proinsulin (>5)
Beta-hydroxy (<2.7)
Glucose increase after glucagon (>25)
Circulating oral hypoglycemic agent (+)
antibody (-)
Example is sulfonylurease (amaril...) stimulate insulin production |
| What are tumors producing IGF-II? | Mainly mesenchymal or hepatic, Solitary fibrous tumor or mesothelioma, or hepatocellular carcinoma, adenocarcinoma, GI, sarcoma, renal carcinoma.
Produce IGF-2 which binds insulin receptor and precipitate hypoglycemia. |
| What are the lab findings caused by tumors producing IGF-2? | Glucose (<55)
Insulin (<3)
C-peptide (<0.2)
Proinsulin (<5)
Beta-hydroxy (<2.7)
Glucose increase after glucagon (>25)
Circulating oral hypoglycemic agent (-)
antibody (-) |
| What are insulin antibodies? | Insulin Autoimmune Syndrome (IAS)
diagnosed by circulating IAA during hypoglycemia, often have an underlying autoimmune disease, and in rare cases it is associated with exogenous insulin admin caused hypoglycemia. |
| What are the lab findings of IAS? | Glucose (<55)
Insulin (>>3)
C-peptide (>>0.2)
Proinsulin (>>5)
Beta-hydroxy (<2.7)
Glucose increase after glucagon (>25)
Circulating oral hypoglycemic agent (-)
antibody (+) |
