MED 4.02 Hyperglycemia and Hypoglycemia PDF

MEDICINE Hyperglycemia and Hypoglycemia Block 4 Oliver Allan Dampil, MD | November 26, 2024 MED 4.02...

MEDICINE Hyperglycemia and Hypoglycemia Block 4 Oliver Allan Dampil, MD | November 26, 2024 MED 4.02 OVERVIEW production, hepatic glycogenolysis, and hepatic (and I. Systemic Glucose Balance B. Common Causes renal) gluconeogenesis and Glucose C. Consequences Hepatic Glycogen stores Counterregulation III. Hypoglycemia ○ Can maintain plasma glucose levels for ~8 h A. Glucose A. Signs and Symptoms ○ Shorter if: B. Physiologic B. Common Causes Glucose demand is increased by exercise Responses C. Consequences Glycogen stores are depleted by illness or II. Hyperglycemia starvation A. Signs and Symptoms B. Physiologic Responses 💬➕ ⭐ LEGEND : Important information : Good-to-know info from lecturer ❗ : Supplementary/Background Info : Exception LEARNING OBJECTIVES Understand the regulation of glucose homeostasis ○ Role of regulatory and counter-regulatory hormones Recognize the signs and symptoms of hyperglycemia and hypoglycemia ○ Know how to elicit these signs and symptoms ○ Understand the pathophysiology of these signs and symptoms Understand the consequences of hyperglycemia and Figure 2. Physiology of Glucose Counterregulation hypoglycemia Apart from glucose production, glucose utilization, and ○ Acute versus chronic insulin secretion, blood glucose levels are also Know the common causes of hyperglycemia and balanced through growth hormone production, cortisol hypoglycemia secretion, and sympathetic response among others I. SYSTEMIC GLUCOSE BALANCE AND GLUCOSE Glucagon increases sugar production, while insulin COUNTERREGULATION promotes the entry of sugar into the cell (Batch 2027) An increase in growth hormone leads to a potent stimulation of IGF-1 and an increase in blood sugar Cortisol can also be increased and there will be a sympathomimetic overflow ○ The signs and symptoms of hypoglycemia (i.e. tremors) are precipitated by this sympathetic outflow. 75% of the glucose is produced by the kidneys Figure 1. Glucose Balance Diagram Table 1. Physiologic Response to Hypoglycemia [Read downwards] Previously thought to be a balance of input and [Batch 2027] output of blood sugar Response when plasma glucose levels decline just below ○ Increased glucose production → Increased the physiologic range glucose utilization → Counterbalance through DECREASED insulin Prolonged hypoglycemia insulin secretion secretion by pancreatic (~4 h) However, it is more complex than this β-cell Increased hepatic Cortisol and growth hormone A. Glucose (Harrison’s, 20th) glycogenolysis and Obligate fuel for the brain under physiologic hepatic and renal Support glucose conditions, however, it can’t synthesize or store its gluconeogenesis production own Decreased glucose Restrict glucose ○ Requires a continuous supply from the arterial utilization in peripheral utilization to a limited circulation tissues = inducing amount (~20% Normal plasma glucose concentration lipolysis and proteolysis compared to ○ Fasting: 70–110 mg/dL (3.9–6.1 mmol/L) (for gluconeogenic epinephrine) ○ After meal: temporarily higher precursors) No role in defense against acute ⭐⭐⭐ Between meals and during fasting: plasma glucose First defense against levels are maintained by endogenous glucose hypoglycemia hypoglycemia Page 1 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Release glucose counterregulatory (plasma glucose-raising) hormones (Figure 3) Adrenomedullary Pancreatic α-cell glucagon epinephrine Stimulates hepatic glycogenolysis and gluconeogenesis Stimulates also renal gluconeogenesis Critical when glucagon is deficient Stimulates lipolysis with the production of glycerol and fatty acids Limits peripheral uptake of glucose Figures 4 and 5. Signs and Symptoms of Diabetes Frequent urination in DM is due to the patient being always thirsty (polydipsia) ○ A result of the sodium-glucose compensatory channels being overwhelmed ○ SGLT receptors exceed their capacity to reabsorb the sugar in the tubules → glucosuria, natriuresis, ↑ urine output (Batch 2027) Figure 3. Physiologic Responses to Decreasing Plasma Glucose Concentrations Exceeding the maximum threshold of the sodium-glucose channels at the proximal However, these thresholds are dynamic. convoluted tubule → cycle of polyuria and ○ Shift to higher-than-normal glucose levels in polydipsia people with poorly controlled diabetes Patients with hyperglycemia or DM are always tired Experience symptoms of hypoglycemia even at and eating more (polyphagia) because glucose fails normal glucose concentration to enter cells ○ Shift to lower-than-normal glucose levels in ○ “Starving in abundance” people with recurrent hypoglycemia ○ The brain keeps on signaling that the person is e.g. patients with intensively treated diabetes hungry, despite abundant glucose in the blood or an insulinoma Numbness, sexual problems, poor wound healing, They have symptoms at glucose levels lower and weight loss are complications than those that cause symptoms in healthy individuals II. HYPERGLYCEMIA A. Signs and Symptoms Some patients can have a blood glucose level as high as 400 mg/dL after a meal, and still not manifest any signs and symptoms ○ Signs and symptoms manifest due to consequences of prolonged hyperglycemia known as diabetes mellitus Figure 6. Signs and Symptoms of Diabetic Ketoacidosis (DKA) In severe cases → DKA (diabetic ketoacidosis) or uncontrolled diabetes B. Common Causes of Hyperglycemia Type 2 Diabetes ○ Most common cause of hyperglycemia In determining the common causes of hyperglycemia, looking at the pathophysiology of diabetes can be useful[Batch 2027]: ○ Insulin resistance ○ Decrease in β-cell function → decrease in insulin in patients with diabetes ○ Problem in the gut microbiome, immune dysregulation, incretin (GLP-1) problems, kidney Page 2 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia problems (due to enhancement of SGLT-2 increasing the reabsorption of sugar), and negative effects on the brain ○ Appetite suppression in hyperglycemia: the higher the sugar, the worse the appetite stimulating effect (vicious cycle) ○ Defects in α-cell → increase glucagon and decrease incretins Disease-related causes[Batch 2027]: ○ Stress hyperglycemia ○ Acute pancreatitis Causes hyperglycemia due to reduced ability to release/produce insulin Iatrogenic causes[Batch 2027]: ○ Drugs-steroids, dopamine, quinolones (gatifloxacin, levofloxacin) ○ Use of dextrose containing fluids in inpatients Figure 8. Complications of hyperglycemia. The signs and symptoms of hyperglycemia secondary to diabetes are actually the complications, such as[Batch 2027]: ○ Skin complications or infections ○ Blurring of vision due to retinopathy ○ Easy fatigability from heart damage ○ Fatty liver ○ Edema from kidney damage and heart failure ○ Osteoporosis III. HYPOGLYCEMIA A. Signs and Symptoms Sympathomimetic responses Figure 7. Problems contributing to hyperglycemia. ○ Sweating ○ Shaking Incretins: Example is glucagon-like peptide-1 (GLP-1) ○ Anxious Adipose, Muscle, Liver: Insulin resistance ○ Dizziness Brain: There is counterproductive increase in appetite ○ Hunger due to increase ○ Tachycardia (fast heartbeat) sugar (vicious cycle) ○ Impaired vision Problems in the kidney may enhance SGLT2, ○ Weakness or fatigue increasing reabsorption of glucose ○ Headache ○ Irritable C. Consequences in Hyperglycemia The classic signs and symptoms of being very hungry Microvascular are similar to those of hypoglycemia[Batch 2027] ○ Retinopathy ○ Nephropathy ○ Neuropathy Macrovascular ○ Cerebrovascular disease ○ Heart disease ○ Peripheral vascular disease Non-vascular[Batch 2027]: ○ Heart failure ○ Sexual problems ○ Dementia Figure 9. Signs and symptoms of hypoglycemia. Page 3 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Table 2. Symptoms of Hypoglycemia histoplasmosis) and Autonomic/ malignancies Adrenergic/ Neurological/Neuroglycopenic (lymphomas, carcinoma Neurogenic breast) Psychiatric Neurological A: Due to increased catabolic requirement[Batch 2027] symptoms symptoms B: Levofloxacin can cause both hyperglycemia and Dizziness and hypoglycemia weakness Sweating Headache Most common cause of hypoglycemia is Paleness Altered, iatrogenic[Batch 2027] Trembling Confusion double or The ff. can also cause hypoglycemia:[Batch 2027] Tachycardia Altered blurred vision ○ Medications that tell the pancreas to make Anxiety behavior Aphasia insulin regardless of the blood sugar Hunger Aggressiveness Dysarthria ○ Injecting Neutral Protamine Hagedorn (NPH) Nausea Slurred speech Motor deficit, Insulin at night Weakness Lapses of unsteady gait, Peaks 4-10 hours after it is given Tingle consciousness lack of ○ Hypoglycemia unawareness coordination Causes of hypoglycemia can also be grouped into Paresthesias endogenous and exogenous causes (Figure 11) Seizures Symptoms of hypoglycemia depend on blood glucose level (e.g., how low the patient’s sugar is) Clinical significance: Case-based application Patient is experiencing neuroglycopenic symptoms such as double vision, aphasic, loss of consciousness Expected level of blood sugar is below 36. Figure 11. Endogenous and exogenous causes of hypoglycemia. HOW DOES CHRONIC KIDNEY DISEASE CAUSE HYPOGLYCEMIA? 25% of gluconeogenesis happens in the kidneys Ability to excrete medications are also impaired due to impaired renal function Figure 10. ⭐Counterregulatory Plasma Glucose Level Classification and Response. ○ Elimination of anti-diabetic agents is prolonged B. Common Causes of Hypoglycemia Table 3. ⭐ Causes of Hypoglycemia IATROGENIC/TREATMENT DISEASE-RELATED RELATED Certain infections with Drugs-quinine, high glucose turnover fluoroquinolones (i.e., malaria) (ciprofloxacin, SepsisA levofloxacinB), Poor oral intake metronidazole, Deranged liver or kidney sulfamethoxazole- function related to acute trimethoprim, or febrile illness Secondary adrenal clarithromycin, tramadol Inadvertent higher dose Figure 12. ⭐ Hypoglycemia associated with glucose-lowering medications. insufficiency associated of insulin or oral drugs with certain infections (i.e., sulfonylureas) (tuberculosis, Page 4 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Figure 13. ⭐ Hypoglycemic effects of nondiabetic medications. ⭐Metformin, GLP-1, TZDs, Alpha-Glucosidase inhibitors, DPP-4 Inhibitors, will only cause hypoglycemia if given with insulin or sulfonylureas[Batch 2027] Other causes of hypoglycemia can be seen in Figure 14 Figure 15. Effects of hypoglycemia on the body. Sustained complications of hypoglycemia are myocardial infarction due to the development of fatal arrhythmia caused by the release of epinephrine and norepinephrine [Batch 2027] Figure 16. Complications and sequelae of hypoglycemia. Figure 14. Causes of hypoglycemia in adults. Source: Harrison’s Principles of Internal Medicine (21st ed) C. Consequences in Hypoglycemia Consequences of HYPERglycemia as more chronic than HYPOglycemia ○ HYPOglycemia can kill you in seconds Aside from the other acute effects of hypoglycemia, the most dreaded complication is death[Batch 2027] ○ Death, coma, heart attack, and stroke can occur if Figure 17. Consequence of chronic hypoglycemia the low blood sugar levels are not resolved Chronic hypoglycemia affects the heart, brain, eyes, Page 5 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia and other regulatory responses (Figure 17) ○ Proatherothrombotic ○ Patients can experience dementia, seizures, ECG Effects of the activation of responses: changes ○ Increase platelet aggregation In the long run, patients can also experience ○ Reduce fibrinolytic balance (increase endothelial dysfunction plasminogen activator inhibitor-1) ↪ More prone to heart attack or stroke ○ Increase intravascular coagulation ○ If a patient is diabetic and is taking medications or Hypoglycemia also reduces protective nitric is not able to eat much, the patient can have oxide-mediated arterial vasodilator mechanisms recurrent inflammation, blood coagulation, and endothelial dysfunction. This can happen due to B. Approach to the Patient with Hypoglycemia the recurrence of hypoglycemia episodes[Batch 2027] Recognition and Documentation Acute symptoms: rhythm abnormalities, Table 5. Signs and Symptoms of Hypoglycemia hemodynamic changes SIGNS AND DESCRIPTION Table 4. Risk factors, complications, and consequences of SYMPTOMS hypoglycemia Hypoglycemia is suspected in RISK FACTORS COMPLICATIONS* patients with: Tight glycemic control ↓ Treatment adherence Typical ○ Confusion Care home residency Cognitive impairment Symptoms ○ Altered level of consciousness Aged 80+ years Hospital admission ○ Seizure Undernutrition Further poor nutrition or Relief of symptoms after the Insulin or sulfonylureas weight loss plasma glucose level is raised[Batch treatment Falls 2027] Polypharmacy Limb fractures Convincing documentation of Joint dislocation Whipple’s Triad hypoglycemia ↓ Activities of daily living ○ Thus, the ideal time to measure (ADL) the plasma glucose level is *Complications can be exacerbated if frail during a symptomatic episode CONSEQUENCES DUE TO FRAILTY Confirms that hypoglycemia is the Further risk of hypoglycemia Low Glucose cause of the symptoms, provided Institutionalization Level the latter resolve after the glucose Increased disability level is raised (i.e., Whipple’s triad) Increased dependency Made while the glucose level is Need for carer support low and before treatment when Premature death the cause of the hypoglycemic Worse clinical outcomes episode is obscure ○ Plasma insulin ○ C-peptide Additional ○ Proinsulin Measurements ○ β-hydroxybutyrate levels Screening for circulating oral hypoglycemic agents and assessment of symptoms before and after the plasma glucose concentration is raised Distinctly Low Plasma Glucose Raises the possibility of an artifact Concentration (pseudohypoglycemia) Without Symptoms Figure 18. Risk factors, complications, and consequences of hypoglycemia. Diagnosis of the Hypoglycemic Mechanism Often deduced from the history, physical IV. CHAPTER 406: HYPOGLYCEMIA (HARRISON’S p. examination, and available laboratory data 3129) Drugs (e.g., alcohol, agents used to treat diabetes) ○ First consideration—even in the absence of TG Note: This section is not part of the lecture and is known use of a relevant drug—given the based on Harrison’s and Batch 2027 Trans. Read at your possibility of surreptitious, accidental, or malicious own discretion. drug administration Other considerations: ○ Evidence of a relevant critical illness A. Etiology and Pathophysiology ○ Hormone deficiencies (less commonly) Hypoglycemia activates the following responses in ○ Non-β-cell tumor that can be pursued T1DM, T2DM, and nondiabetic individuals: diagnostically (rarely) ○ Proinflammatory ○ Procoagulant Page 6 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Urgent Treatment of glucose may be necessary for some patients. Raise plasma glucose concentrations only transiently Table 7. Recalls[Batch 2027] ○ Patients should therefore be urged to eat as soon Drugs used to treat DM, Most CC (common cause) of as is practical to replete glycogen stores exposure to other drugs hypoglycemia (alcohol) Table 6. Treatment for Hypoglycemia Serious illnesses such as TREATMENT DESCRIPTION Second only to drugs as renal, hepatic, or cardiac Glucose Tablets or Oral treatment for patients causes of hypoglycemia failure, sepsis, and inanition Glucose-Containing that are able and willing 1. Symptoms Fluids, Candy, or Reasonable initial dose: 15-20 consistent with Food g of glucose hypoglycemia For patients that are unable or 2. Low plasma unwilling (because of Whipple’s Triad glucose measured with a neuroglycopenia) precise method IV administration of glucose 3. Relief of symptoms Parenteral Therapy (25 g) followed by a glucose after the plasma glucose infusion guided by serial level is raised plasma glucose Lower limit of the fasting measurements Approximately 70 mg/dL plasma glucose If IV therapy is not practical (3.9 mmol/L) concentration 1.0 mg in adults, particularly Obligate metabolic fuel for Glucose (may also use in patients with T1DM the brain under physiologic ketones in prolonged fasting Acts by stimulating conditions after two weeks) glycogenolysis Hepatic glycogen stores are Subcutaneous or ○ Ineffective in able to sustain glucose Approximately ~8 h Intramuscular glycogen-depleted needs for Glucagon individuals (e.g., those with Glycemic maintenance goals alcohol-induced 140-180 mg/dL in hospitalized patients hypoglycemia) First defense against Stimulates insulin secretion Decreased insulin hypoglycemia ○ Less useful in T2DM Second defense against Somatostatin analogue Increase glucagon hypoglycemia Used to suppress insulin Increased epinephrine Octreotide secretion in Third defense against (critical when glucagon is sulfonylurea-induced hypoglycemia deficient) hypoglycemia Loss of the warning adrenergic and cholinergic Prevention of Recurrent Hypoglycemia symptoms that previously Offending drugs can be discontinued or their doses allowed the patient to reduced Hypoglycemia unawareness recognize developing Underlying critical illnesses can often be treated hypoglycemia and therefore Cortisol and growth hormone can be replaced if to abort the episode by levels are deficient ingesting carbohydrates Surgical, radiotherapeutic, or chemotherapeutic reduction of a non-islet cell tumor REFERENCES ○ Can alleviate hypoglycemia even if the tumor Dampil, Oliver Allan, MD. Notes from Hyperglycemia cannot be cured and Hypoglycemia Glucocorticoid or growth hormone administration Harrison’s Principles of Internal Medicine (21st ed). ○ Reduce hypoglycemic episodes in patients with non-islet cell tumor REVIEW QUESTIONS Surgical resection of an insulinoma is curative ○ If not possible in patients with a no- tumor β-cell 1. What is the primary defense mechanism against a disorder: medical therapy with diazoxide or decline in plasma glucose levels just below the octreotide physiologic range? Partial pancreatectomy in patients with a nontumor β-cell disorder A. Increased insulin secretion by pancreatic β-cells The treatment of autoimmune hypoglycemia (e.g., B. Increased hepatic glycogenolysis and renal with glucocorticoid or immunosuppressive drugs) is gluconeogenesis problematic, but these disorders are sometimes C. Decreased insulin secretion by pancreatic β-cells self-limited. D. Increased cortisol and growth hormone secretion ○ Failing these treatments, frequent feedings and avoidance of fasting may be required. 2. Which of the following best explains the physiology of ○ Administration of uncooked cornstarch at the classic symptoms of polyuria and polydipsia in bedtime or even an overnight intragastric infusion Page 7 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia diabetes mellitus? B. Sulfonylureas C. Quinine A. Increased production of cortisol and growth hormone D. Metformin B. Stimulation of hepatic glycogenolysis and gluconeogenesis 9. Convincing documentation of hyperglycemia requires C. Exceeding the reabsorption threshold of glucose in the the fulfillment of Whipple’s triad. Thus, the ideal time to proximal tubule measure the plasma glucose level is after a symptomatic D. Sympathetic nervous system activation due to episode. hypoglycemia A. Only the first statement is correct. 3. A 40-year-old patient with diabetes is brought to the B. Only the second statement is correct. emergency room after feeling lightheaded and confused. C. Both statements are correct. A glucose test reveals a plasma glucose level of 50 D. Both statements are incorrect. mg/dL. Which of the following physiological responses is most likely to have been triggered at this glucose level? 10. Which of the following treatments for hypoglycemia is incorrectly matched? A. Release of endogenous insulin B. Release of glucagon and adrenaline A. 1.0 mg SC or IM glucagon :: adult patients with T1DM C. Onset of autonomic symptoms B. IV administration of 25 g glucose :: patient with D. Cognitive deterioration neuroglycopenia C. Oral treatment of 15-20 g glucose :: patients with 4. A 25-year-old man presents with seizures after sulfonylurea-induced hypoglycemia skipping meals for 24 hours. A glucose test reveals a D. NOTA plasma glucose level of 18 mg/dL. What is the most likely classification of his condition? RATIONALE A. Hypoglycemia 1. C. The first defense mechanism against declining B. Symptomatic hypoglycemia plasma glucose is the suppression of insulin secretion, C. Neuroglycopenia which reduces glucose uptake by peripheral tissues, D. Severe neuroglycopenia conserving glucose for vital organs like the brain. 5. A 60-year-old woman with a history of diabetes 2. C. In diabetes mellitus, hyperglycemia overwhelms the reports shakiness, sweating, and a rapid heartbeat. Her sodium-glucose transporters in the proximal tubule, plasma glucose level is measured at 72 mg/dL. Which of causing glucosuria. The resulting osmotic diuresis leads the following counterregulatory responses is most likely to increased urination (polyuria) and excessive thirst occurring at this stage? (polydipsia). A. Release of growth hormone 3. C. Onset of autonomic symptoms B. Release of cortisol This corresponds to the plasma glucose threshold of 54 C. Release of glucagon and adrenaline mg/dL as indicated in Figure 10. D. Cognitive deterioration 4. D. Severe neuroglycopenia 6. A 35-year-old man complains of dizziness and This corresponds to the plasma glucose threshold of 18 difficulty concentrating during a fasting test. His plasma mg/dL and is associated with severe outcomes such as glucose level is measured at 36 mg/dL. What coma or seizures. physiological consequence is most likely occurring at this glucose level? 5. C. Release of glucagon and adrenaline This corresponds to the plasma glucose threshold of 72 A. Onset of autonomic symptoms mg/dL, where these hormones are released to counteract B. Cognitive deterioration hypoglycemia. C. Release of glucagon and adrenaline D. Coma, seizures 6. B. Cognitive deterioration This corresponds to the plasma glucose threshold of 36 7. All of the following cause hypoglycemia except: mg/dL, where neuroglycopenia leads to cognitive impairment. A. Polypharmacy B. Too much insulin 7. C. Acute pancreatitis causes hyperglycemia. C. Acute pancreatitis D. Chronic kidney disease 8. D. Metformin, GLP-1, TZDs, Alpha-Glucosidase inhibitors, DPP-4 Inhibitors, will only cause hypoglycemia 8. Which if the following drugs if taken as a monotherapy if given with insulin or sulfonylureas. would not produce hypoglycemia? 9. D. Whipple’s triad confirms hypoglycemia, not A. Insulin Page 8 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Critical when glucagon hyperglycemia. The ideal time to measure the plasma is deficient glucose level is during a symptomatic episode, not after. Stimulates lipolysis with the production of 10. C. The treatment for patients with glycerol and fatty acids sulfonylurea-induced hypoglycemia is Octreotide. Oral Limits peripheral treatment of 15-20 g glucose with glucose tablets, uptake of glucose glucose-containing fluids, candy, or food is for patients that are able and willing. SIGNS AND SYMPTOMS OF HYPERGLYCEMIA Diabetes Mellitus Diabetic Ketoacidosis SUMMARY Very thirsty (polydipsia) Very hungry SYSTEMIC GLUCOSE BALANCE AND GLUCOSE (polyphagia) COUNTERREGULATION Polyuria, polydipsia, Frequent urination enuresis (polyuria) Glucose (Harrison’s, 20th) Dehydration, Dry skin Obligate fuel for the brain under physiologic tachycardia, orthostasis Drowsiness and fatigue conditions, however, it can’t synthesize or store its Abdominal pain, Blurry vision own nausea, vomiting Infections or injuries Normal plasma glucose concentration Fruity, acetone breath heal more slowly than ○ Fasting: 70–110 mg/dL (3.9–6.1 mmol/L) Kussmaul breathing usual ○ After meal: temporarily higher Mental status changes Sudden weight loss (combative, drunk, Sexual problems Physiology of Glucose Counterregulation coma) Numb or tingling hands or feet Vaginal infections COMMON CAUSES OF HYPERGLYCEMIA Most common cause: Type 2 Diabetes Response when plasma glucose levels decline just below the physiologic range DECREASED insulin Prolonged hypoglycemia CONSEQUENCES OF HYPERGLYCEMIA secretion by pancreatic (~4 h) β-cell Microvascular Macrovascular Increased hepatic Cortisol and growth hormone Cerebrovascular glycogenolysis and Retinopathy disease renal Support glucose hepatic and production Nephropathy Heart disease gluconeogenesis Neuropathy Peripheral vascular glucose Restrict glucose Decreased utilization to a limited disease utilization in peripheral tissues = inducing amount (~20% lipolysis and proteolysis compared to HYPOGLYCEMIA (for gluconeogenic epinephrine) precursors) No role in defense SIGNS AND SYMPTOMS OF HYPOGLYCEMIA against acute hypoglycemia ⭐⭐⭐ First defense against hypoglycemia Autonomic/ Adrenergic/ Neurological/Neuroglycopenic Release glucose counterregulatory (plasma Neurogenic glucose-raising) hormones (Figure 3) Sweating Adrenomedullary Paleness Pancreatic α-cell glucagon epinephrine Trembling Psychiatric Neurological Stimulates hepatic glycogenolysis and gluconeogenesis Tachycardia symptoms symptoms Stimulates also renal Anxiety gluconeogenesis Hunger Page 9 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Nausea Dizziness and Weakness weakness Tingle Headache Altered, Confusion double or Altered blurred vision behavior Aphasia Aggressiveness Dysarthria Slurred speech Motor deficit, Lapses of unsteady gait, consciousness lack of coordination Paresthesias Seizures Metformin, GLP-1, TZDs, Alpha-Glucosidase inhibitors, DPP-4 Inhibitors, will only cause hypoglycemia if given with insulin or sulfonylureas Hypoglycemic Effects of Non-diabetic Medications CAUSES OF HYPOGLYCEMIA Iatrogenic/Treatment Disease Related Related Certain infections with Drugs-quinine, high glucose turnover fluoroquinolones Other Causes (i.e., malaria) (ciprofloxacin, SepsisA levofloxacinB), Medications that tell the pancreas to make insulin Poor oral intake metronidazole, regardless of the blood sugar Deranged liver or kidney sulfamethoxazole- Injecting Neutral Protamine Hagedorn (NPH) function related to acute trimethoprim, Insulin at night or febrile illness clarithromycin, tramadol ○ Peaks 4-10 hours after it is given Secondary adrenal Inadvertent higher dose Hypoglycemia unawareness insufficiency associated of insulin or oral drugs with certain infections (i.e., sulfonylureas) CONSEQUENCES OF HYPOGLYCEMIA (tuberculosis, histoplasmosis) and malignancies (lymphomas, carcinoma breast) Endogenous and Exogenouse Causes Hypoglycemia Associated with Glucose-Lowering Medications Page 10 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Recognition and Documentation SIGNS AND SYMPTOMS DESCRIPTION Hypoglycemia is suspected in patients with: Typical Symptoms ○ Confusion ○ Altered level of consciousness ○ Seizure Relief of symptoms after the plasma glucose level is raised[Batch 2027] Convincing documentation of hypoglycemia Chronic hypoglycemia affects the heart, brain, eyes, Whipple’s Triad ○ Thus, the ideal and other regulatory responses time to measure ○ Patients can experience dementia, seizures, ECG the plasma changes glucose level is In the long run, patients can also experience during a endothelial dysfunction symptomatic ↪ More prone to heart attack or stroke episode ○ If a patient is diabetic and is taking medications or is not able to eat much, the patient can have Confirms that recurrent inflammation, blood coagulation, and hypoglycemia is the endothelial dysfunction. This can happen due to cause of the the recurrence of hypoglycemia episodes[Batch 2027] symptoms, provided Low Glucose Level Acute symptoms: rhythm abnormalities, the latter resolve after hemodynamic changes the glucose level is raised (i.e., Whipple’s Risk Factors Complications* triad) Tight glycemic control ↓ Treatment adherence Made while the Care home residency Cognitive impairment glucose level is low Aged 80+ years Hospital admission and before treatment Undernutrition Further poor nutrition or when the cause of the Insulin or sulfonylureas weight loss hypoglycemic episode treatment Falls is obscure Polypharmacy Limb fractures ○ Plasma insulin Joint dislocation ○ C-peptide ↓ Activities of daily living ○ Proinsulin (ADL) Additional Measurements ○ β-hydroxybutyrat *Complications can be exacerbated if frail e levels Consequences Due to Frailty Screening for Further risk of hypoglycemia circulating oral Institutionalization hypoglycemic agents Increased disability and assessment of Increased dependency symptoms before and Need for carer support after the plasma Premature death glucose concentration Worse clinical outcomes is raised Raises the possibility HYPOGLYCEMIA [Harrison’s, 20th] Distinctly Low Plasma of an artifact Glucose Concentration (pseudohypoglycemi Etiology and Pathophysiology Without Symptoms a) Activates the proinflammatory, procoagulant, and Diagnosis of the Hypoglycemic Mechanism proatherothrombotic responses in T1DM, T2DM, and Deduced from the history, physical examination, and nondiabetic individuals available laboratory data Increases platelet aggregation First consideration: Drugs (e.g., alcohol, agents used to Reduces fibrinolytic balance (increases plasminogen treat diabetes) activator inhibitor-1) Other considerations: Increases intravascular coagulation ○ Evidence of a relevant critical illness Reduces protective nitric oxide-mediated arterial ○ Hormone deficiencies vasodilator mechanisms ○ Non-β-cell tumor that can be pursued Approach to the Patient with Hypoglycemia diagnostically Page 11 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia Urgent Treatment TREATMENT DESCRIPTION Oral treatment for patients that are able Glucose Tablets or and willing Glucose-Containing Fluids, Reasonable initial Candy, or Food dose: 15-20 g of glucose For patients that are unable or unwilling (because of neuroglycopenia) IV administration of Parenteral Therapy glucose (25 g) followed by a glucose infusion guided by serial plasma glucose measurements If IV therapy is not practical 1.0 mg in adults, particularly in patients with T1DM Acts by stimulating glycogenolysis ○ Ineffective in Subcutaneous or glycogen-depleted Intramuscular Glucagon individuals (e.g., those with alcohol-induced hypoglycemia) Stimulates insulin secretion ○ Less useful in T2DM Somatostatin analogue Used to suppress Octreotide insulin secretion in sulfonylurea-induced hypoglycemia Prevention of Recurrent Hypoglycemia Offending drugs can be discontinued or their doses reduced Underlying critical illnesses can often be treated Cortisol and growth hormone can be replaced if levels are deficient Surgical, radiotherapeutic, or chemotherapeutic reduction of a non-islet cell tumor Glucocorticoid or growth hormone administration Surgical resection of an insulinoma Partial pancreatectomy in patients with a nontumor β-cell disorder Treatment of autoimmune hypoglycemia (e.g., with glucocorticoid or immunosuppressive drugs) Page 12 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina  MED 4.02 Hyperglycemia and Hypoglycemia APPENDIX Page 13 of 13 | TH: ZUÑIGA, K. | RTG3 | NACULANGGA, TUBAON, YAP. Checked & Verified: MJ&Zarina