Diabetes Mellitus (DM) ADA) defines DM

A

Diabetes Mellitus (DM)

Definition

• ▪ 
  The American Diabetes Association (ADA) defines DM as follows:
  • • 
    FPG ≥126 mg/dL, which should be confirmed with repeat testing on a different day. Fasting is defined as no caloric intake for at least 8 hr.
  • • 
    Sx of hyperglycemia and a casual (random) plasma glucose ≥200 mg/dL. Classic sx of hyperglycemia include polyuria, polydipsia, and unexplained weight loss.
  • • 
    An OGTT with a plasma glucose ≥200 mg/dL 2 hr after a 75-g (100 g for pregnant women) glucose load
  • • 
    HBA _1c ≥6.5%
• ▪ 
  Prediabetes: glucose levels > nl but not high enough to meet the criteria for dx DM
  • • 
    Impaired fasting glucose: FBS 100 to 125 mg/dL
  • • 
    Impaired glucose tolerance: after OGTT, a 2-hr plasma glucose 140 to 199 mg/dL
  • • 
    HBA _1c value 5.7% to 6.4%
• ▪ 
  Table 5-1 describes diagnostic categories for diabetes mellitus and at-risk states. 
  TABLE 5-1

  General Comparison of the Two Types of Diabetes Mellitus

  	Type 1	Type 2
  Previous terminology	Insulin-dependent diabetes mellitus (IDDM), type I, juvenile-onset diabetes	Non–insulin-dependent diabetes mellitus, type II, adult-onset diabetes
  Age at onset	Usually <30 yr, particularly childhood and adolescence, but any age	Usually >40 yr, but any age
  Genetic predisposition	Moderate; environmental factors required for expression; 35%-50% concordance in monozygotic twins; several candidate genes proposed	Strong; 6%-90% concordance in monozygotic twins; many candidate genes proposed; some genes identified in maturity-onset diabetes of the young
  Human leukocyte antigen associations	Linkage to DQA and DQB, influenced by DRB (3 and 4) (DR2 protective)	None known
  Other associations	Autoimmune; Graves’ disease, Hashimoto’s thyroiditis, vitiligo, Addison’s disease, pernicious anemia	Heterogeneous group, ongoing subclassification based on identification of specific pathogenic processes and genetic defects
  Precipitating and risk factors	Largely unknown; microbial, chemical, dietary, other	Age, obesity (central), sedentary lifestyle, previous gestational diabetes
  Findings at diagnosis	85%-90% of patients have one and usually more autoantibodies to ICA512/Ia-2/IA-2β, GAD 65 , insulin (IAA)	Possibly complications (microvascular or macrovascular) caused by significant preceding asymptomatic period
  Endogenous insulin levels	Low or absent	Usually present (relative deficiency), early hyperinsulinemia
  Insulin resistance	Only with hyperglycemia	Mostly present
  Prolonged fast	Hyperglycemia, ketoacidosis	Euglycemia
  Stress, withdrawal of insulin	Ketoacidosis	Nonketotic hyperglycemia, occasionally ketoacidosis

  
  

  GAD, glutamic acid decarboxylase; IA-2/IA-2β, tyrosine phosphatases; IAA, insulin autoantibodies, ICA, islet cell antibody; ICA512, islet cell autoantigen 512 (fragment of IA-2).

  From Andreoli TE (ed): Cecil Essentials of Medicine, 6th ed. Philadelphia, Saunders, 2005.

PE

Diabetic Retinopathy

• a. 
  Nonproliferative (background diabetic retinopathy)
  • i. 
    Initially: microaneurysms, capillary dilation, waxy or hard exudates, dot and flame hemorrhages, atrioventricular shunts
  • ii. 
    Advanced stage: microinfarcts with cotton wool exudates, macular edema
• b. 
  Proliferative retinopathy: formation of new vessels, vitreous hemorrhages, fibrous scarring, and retinal detachment

Diabetic Neuropathy

• a. 
  Distal sensorimotor polyneuropathy
  • i. 
    Sx: paresthesia, hyperesthesia, or burning pain involving bilateral distal extremities, in a “stocking-glove” distribution. It can progress to motor weakness and ataxia.
  • ii. 
    PE: ↓ pinprick sensation, sensation to light touch, vibration sense, and loss of proprioception. ↓ DTRs and atrophy of interossei muscles can also be seen.
• b. 
  Autonomic neuropathy
  • i. 
    GI: esophageal motility abnlities, gastroparesis, diarrhea (usually nocturnal)
  • ii. 
    GU: neurogenic bladder (hesitancy, weak stream, and dribbling), impotence
  • iii. 
    Orthostatic hypotension: postural syncope, dizziness, lightheadedness
• c. 
  Polyradiculopathy: painful weakness and atrophy in the distribution of ≥1 contiguous nerve roots
• d. 
  Mononeuropathy involving cranial nerves III, IV, or VI or peripheral nerves

Diabetic Nephropathy

Pts have pedal edema, pallor, weakness, uremic appearance.

Foot Ulcers

They occur in 15% of individuals with DM (incidence rate, 2%/yr) → leading causes of hospitalization and amputation in U.S. They result from combination of PVD, repeated trauma (unrecognized because of sensory loss), and superimposed infection.

• a. 
  Sx: less than would be expected from clinical findings, resulting from loss of sensation related to peripheral neuropathy
• b. 
  Dx: assessment of pedal pulses, sensation (using a 10-g monofilament)
• c. 
  Prevention: strict glucose control, pt education, prescription footwear, podiatric care, evaluation for surgical interventions

Neuropathic Arthropathy (Charcot’s Joints)

Bone or joint deformities result from repeated trauma (secondary to peripheral neuropathy).

Necrobiosis Lipoidica Diabeticorum

Plaquelike reddened areas with a central area that fades to white yellow are found on the anterior surfaces of the legs.

Detection and DX of Gestational DM (GDM)

• ▪ 
  OGTT
• ▪ 
  Women with GDM should be screened for diabetes 6 to 12 wk post partum.

Lab Screening in Diabetics

• ▪ 
  Screening for diabetic retinopathy: Alb/Cr ratio (microalb) in a random spot urine collection or by 24-hr urine collection for alb, CrCl
• ▪ 
  Dx of microalbuminuria (30-299 mg/24 hr) should be based on 2 to 3 ↑ levels within a 3- to 6-mo period because of marked variability in day-to-day alb excretion
• ▪ 
  Labs in DM: HBA _1c , urine microalbumin, fasting lipid panel, serum Cr, and electrolytes; TSH, vitamin B ₁₂level, IgA TTG Ab (for celiac disease screen) in type 1 DM
• ▪ 
  Daily monitoring with glucose test strips: type 1 DM and pregnant women on insulin ≥3 ×/day. T2 DM not on insulin, 1-2×/day

Treatment

ADA and European Association for the Study of Diabetes recommend: “Intervention at the time of Dx with metformin in combination with life style changes (diet and exercise) and continuing timely augmentation of Rx with additional agents (including early initiation of insulin Rx) as a means of achieving adequate glycemic control

• 1. 
  Diet
  • a. 
    Calories
    • i. 
      Start with 15 calories/lb of ideal body weight; ↑ 20 calories/lb for an active person and 25 calories/lb if the pt does heavy physical labor.
    • ii. 
      The calories are distributed as 45% to 65% carbohydrates; <30% fat, with saturated fat limited to <7% of total calories; and 10% to 30% protein; daily cholesterol <300 mg.
    • iii. 
      The emphasis should be on complex carbohydrates rather than simple and refined starches and on polyunsaturated instead of saturated fats in a ratio of 2:1.
    • iv. 
      The glycemic index compares the ↑ in blood sugar after the ingestion of simple sugars and complex carbohydrates with the ↑ that occurs after the absorption of.
• 2. 
  Exercise: Exercise program must be individualized and built up slowly. Consider beginning with 15 min of low-impact aerobic exercise 3 ×/wk and increasing the frequency and duration to 30 to 45 min of moderate aerobic activity (50% to 70% of maximum age predicted heart rate) to 3 to 5 days/wk. In the absence of contraindications, resistance training 3 ×/wk should be encouraged.
• 3. 
  Weight loss : to ideal body weight if the pt is overweight
  • • 
    Maintain HbA _1c <7%. HbA _1c 7.5 or higher may be reasonable in elderly pts with limited life expectancy and ↑ risk of hypoglycemia.
  • • 
    When the previous measures fail, oral hypoglycemic agents ( Table 5-2 ) should be added to the regimen in type 2 DM. If renal function is not significantly impaired (creat < 1.3), metformin is the preferred initial hypoglycemic agent. GLP-1 agonists and dipeptidyl peptidase-4 inhibitions are preferred as additional oral hypoglycemics but cost is a limiting factor, especially in elderly patients. 
    TABLE 5-2

    Oral Antidiabetic Agents and Monotherapy

    	Sulfonylureas	Biguanides	α-Glucosidase Inhibitors	Incretin Mimetics	Meglitinides	Dipeptidyl Peptidase-4 Inhibitor
    Generic name	Glimepiride, glyburide, glipizide, chlorpropamide, tolbutamide	Metformin	Acarbose, miglitol	Exanatide, liraglutide	Repaglinide, nateglinide	Sitagliptin, linagliptin, saxagliptin
    Mode of action	↑↑ Pancreatic insulin secretion chronically	↓↓HGP; ↓ peripheral IR; ↓ intestinal glucose absorption	Delays PP digestion of carbohydrates and absorption of glucose	↑ Insulin secretion	↑↑ Pancreatic insulin secretion acutely	Potentiates insulin synthesis and release
    Preferred patient type	Diagnosis age >30 yr, lean, diabetes <5 yr, insulinopenic	Overweight, IR, fasting hyperglycemia, dyslipidemia	PP hyperglycemia	Type 2 DM	PP hyperglycemia, insulinopenic
    Therapeutic effects
    ↓ HBA 1c ∗ (%)	1-2	1-2	0.5-1	↓ HBA1c by 0.7 -0.9	1-2	↓ HBA 1cby 0.5%
    ↓ FPG ∗ (mg/dL)	50-70	50-80	15-30		40-80
    ↓ PPG ∗ (mg/dL)	≈90	80	40-50		30
    Insulin levels	↑	—	—		↑
    Weight	↑	—/↓	—		↑
    Lipids	—	↓ LDL ↓↓TG			—
    Side effects	Hypoglycemia	Diarrhea, lactic acidosis	Abdominal pain, flatulence, diarrhea	Nausea, headache, diarrhea	Hypoglycemia (low risk)
    Dose(s)/day	1-3	2-3	1-3	Variable from daily to weekly	1-4+	1
    Maximum daily dose (mg)	Depends on agent	2550	150 (<60-kg BW) 300 (>60-kg BW)		16 (repaglinide) 360 (nateglinide)	100
    Range/dose (mg)	Depends on agent	500-1000	25-50 (<60-kg BW) 25-100 (>60-kg BW)		0.5-4 (repaglinide) 60, 120 (nateglinide)	50-100
    Optimal administration time	≈30 min premeal (some with food, others on empty stomach)	With meal	With first bite of meal		Preferably <15 (0-30 min) before meals (omit if no meal)
    Main site of metabolism/excretion	Hepatic/renal, fecal	Not metabolized/renal	Only 2% absorbed/fecal	Renal	Hepatic/fecal

    
    

    HGP, Hepatic glucose production; IR, insulin resistance; PP, postprandial; PPG , postprandial plasma glucose.

    From Andreoli TE (ed): Cecil Essentials of Medicine, 6th ed. Philadelphia, Saunders, 2005.

    ∗ Values combined from numerous studies; values are also dose dependent.
  • • 
    Insulin: indicated for all pts with type 1 DM and for pts with type 2 DM whose condition cannot be adequately controlled with diet and oral agents. Insulin Rx may be started with oral agents at 0.3 unit/kg, or as replacement, starting at 0.6 to 1 unit/kg. Table 5-3 describes commonly used types of insulin.
    • a. 
      The risks of insulin Rx include weight gain, hypoglycemia, and in rare cases, allergic or cutaneous reactions.
    • b. 
      Replacement insulin Rx should mimic nl release patterns.
      • i. 
        50% to 60% of daily insulin can be given as a long-acting insulin (NPH, ultralente, glargine, detemir) injected qd or bid.
      • ii. 
        40% to 50% can be short-acting (regular) or rapid-acting (lispro, aspart, glulisine) to cover mealtime carbohydrates and correct ↑ current glucose levels.
    TABLE 5-3

    Types of Insulin

    Preparation	Brand	Onset (hr)	Peak (hr)	Duration (hr)	Route
    Insulin aspart	NovoLog †	<0.25	1-3	3-5	SC
    Insulin aspart protamine/insulin aspart	NovoLog Mix 70/30 †	<0.25	1-4	24	SC
    Insulin detemir	Levemir ‡	1	None	24	SC
    Insulin glargine	Lantus †	1.1	None	≥24	SC
    Insulin glulisine	Apidra †	≤0.25	1	2-4	SC, IV §
    Insulin lispro	Humalog †	<0.25	1	3.5-4.5	SC
    Insulin lispro protamine/insulin lispro	Humalog Mix 75/25 †	≤0.25	0.5-1.5	24	SC
    	Humalog Mix 50/50 †	≤0.25	1	16	SC
    Insulin injection regular (R)	Humulin R ∗	0.5	2-4	6-8	SC, IM, IV
    	Novolin R ‡	0.5	2.5-5	8	SC, IM, IV
    Insulin isophane suspension (NPH)/regular insulin (R)	Humulin 70/30 ∗	0.5	2-12	24	SC
    	Humulin 50/50 ∗	0.5	3-5	24	SC
    	Novolin 70/30 ‡	0.5	2-12	24	SC
    Insulin isophane suspension (NPH)	Humulin N ∗	1-2	6-12	18-24	SC
    	Novolin N ‡	1.5	4-12	24	SC

    Injectable insulins listed are available in a concentration of 100 units/mL; Humulin R, in a concentration of 500 unit/mL for SC injection only, is available by prescription from Lilly for insulin-resistant patients who are hospitalized or under close medical supervision.

    From Ferri FF: Ferri’s Clinical Advisor 2010. Philadelphia, Mosby, 2010.

    ∗ Recombinant (using E. coli ). 

    † Recombinant human insulin analogue (using E. coli ). 

    ‡ Recombinant (using S. cerevisiae ). 

    § IV to be used in a clinical setting under proper medical supervision.
  • • 
    Continuous subcutaneous insulin infusion (CSII, or insulin pump) provides better glycemic control than does conventional Rx. It should be considered for DM in childhood or adolescence and during pregnancy.
  • • 
    The Diabetes Control and Complications Trial (DCCT) showed that intensive Rx for glucose control ↓ the development and progression of complications of type 1 DM. In this trial, the risks for retinopathy, nephropathy, and neuropathy were ↓ by 70%, 54%, and 64%, respectively.
  • • 
    Low-dose aspirin (ASA; 81 mg/day): for primary prevention in diabetic pts with one additional CV risk factor, including age >40 yr, cigarette smoking, HTN, obesity, albuminuria, hyperlipidemia, and family hx of CAD
  • • 
    Statins: DM >40 yr with ≥1 risk factor for CAD; LDL goal <100 mg/dL, <70 mg/dL if overt CAD
  • • 
    BP control: SBP <130 DBP <80 mm Hg. Use ACEI to ↓ albuminuria and prevent CKD regardless of presence of HTN.
  • • 
    Bariatric surgery: consider in adults with BMI >35 kg/m ² and type 2 diabetes
  • • 
    Hypoglycemia Rx: conscious person → glucose tab or gel 15 to 20 g; unconscious → IM glucagon
  • • 
    Neuropathy Rx: duloxetine, pregabalin, gabapentin
  • • 
    Diabetic gastroparesis Rx: endoscopic injection of botulinum toxin into the pylorus and gastric electrical stimulation (using f electrodes placed laparoscopically in the muscle wall of the stomach antrum and connected to a neurostimulator)
  • • 
    Nephropathy: ACEIs or ARBs (if intolerant to ACEIs)
  • • 
    Glycemic control in hospitalized pts: Avoid intensive insulin Rx. The ACP recommends a target blood glucose level of 140 to 200 mg/dL if insulin Rx is used. Table 5-4 describes an insulin sliding scale. 
    TABLE 5-4

    Regular Insulin (SC) Sliding Scale

    Finger Stick Blood Glucose	Mild Scale	Moderate Scale	Aggressive Scale
    <60	1 amp (25 g) D50 or orange juice, call MD	1 amp D50 or orange juice, call MD	1 amp D50 or orange juice, call MD
    60-150	No insulin	No insulin	No insulin
    151-200	No insulin	3 units	4 units
    201-250	2 units	5 units	6 units
    251-300	4 units	7 units	10 units
    301-350	6 units	9 units	12 units
    351-400	8 units	11 units	15 units
    >400	10 units, call physician	13 units, call physician	18 units, call physician

    
    

    From Nguyen TC, Abilez OJ (eds): Practical Guide to the Care of the Surgical Patient: The Pocket Scalpel. Philadelphia, Mosby, 2009.

1

Diabetic Ketoacidosis

Metabolic decompensation in diabetic pts usually precipitated by an infectious process (≤40% of cases). Poor compliance w/insulin Rx and severe medical illness (e.g., CVA, MI) are other common causes. Consider cocaine abuse in middle age DM w/multiple DKA admissions.

Diagnosis

PE

• ▪ 
  Evidence of dehydration (tachycardia, hypotension, dry mucous membranes, sunken eyeballs, poor skin turgor)
• ▪ 
  Clouding of mental status
• ▪ 
  Tachypnea w/air hunger (Kussmaul’s respiration)
• ▪ 
  Fruity breath odor (caused by acetone)
• ▪ 
  Lipemia retinalis in some pts
• ▪ 
  Possible evidence of precipitating factors (infected wound, pneumonia)
• ▪ 
  Abd tenderness in some pts

Labs

• ▪ 
  Glucose level is generally >250 mg/dL; urine and serum ketones (+) (usually 7-10 mmol/L).
• ▪ 
  ABGs reveal acidosis: arterial pH usually <7.30 w/Pco ₂ >40 mm Hg.
• ▪ 
  Serum electrolytes:
  • • 
    Serum bicarbonate is usually <18 mEq/L.
  • • 
    Serum K ⁺ : may be ↓, nl, or ↑. There is always significant total body K ⁺ depletion regardless of the K ⁺level.
  • • 
    Serum Na ⁺ : usually ↓ (pseudohyponatremia) as a result of ↑↑ glucose, dehydration, and lipemia. Assume 1.6 mEq/L ↓ in extracellular Na ⁺ for each 100 mg/dL↑ in glucose.
  • • 
    Calculate the AG: AG = Na ⁺ − (Cl ⁻ + HCO ₃ ⁻ ).
  • • 
    In DKA, the AG is ↑ (generally >15); hyperchloremic metabolic acidosis may be present in unusual circumstances when both the GFR and the plasma volume are well maintained.
• ▪ 
  CBC w/diff, U/A, urine and blood cultures to r/o infectious precipitating factor
• ▪ 
  Serum Ca ²⁺ , Mg ²⁺ , and PO ₄ ^-3 ; plasma PO ₄ ^-3 and Mg ²⁺ levels may be significantly depressed and should be rechecked within 24 hr because they may ↓ further w/correction of DKA.
• ▪ 
  ↑ BUN and Cr secondary to significant dehydration
• ▪ 
  Amylase, LFTs should be checked in pts w/abd pain.

Imaging

CXR is helpful to r/o infectious process. The initial CXR may be nl if the pt has significant dehydration. Repeat CXR after 24 hr if pulmonary infection is strongly suspected.

Treatment

• ▪ 
  Fluid replacement (the usual deficit is 6-8 L), insulin Rx, electrolyte replacement
• ▪ 
  Consider bicarbonate Rx ( Fig. 5-1 ). 
  
  

  FIGURE 5-1

  Management of DKA and HHS.

  (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)

2

Hyperosmolar Non-Ketotic Coma, Honk

Definition

This is a state of extreme hyperglycemia, marked dehydration, serum hyperosmolarity, mental status changes, and absence of ketoacidosis.

Etiology

• ▪ 
  Infections, 20% to 25% (e.g., pneumonia, UTI, sepsis)
• ▪ 
  New or previously unrecognized diabetes (30%-50%)
• ▪ 
  Reduction or omission of diabetic medication
• ▪ 
  Stress (MI, CVA)
• ▪ 
  Drugs: diuretics (dehydration), phenytoin, diazoxide (impaired insulin secretion)

Diagnosis

H&P

• ▪ 
  Evidence of extreme dehydration (poor skin turgor, sunken eyeballs, dry mucous membranes)
• ▪ 
  Neurologic defects (reversible hemiplegia, focal seizures)
• ▪ 
  Orthostatic hypotension, tachycardia
• ▪ 
  Evidence of precipitating factors (pneumonia, infected skin ulcer)
• ▪ 
  Coma (25% of pts), delirium

Labs

• ▪ 
  Hyperglycemia: serum glucose usually >600 mg/dL
• ▪ 
  Hyperosmolarity: serum osmolarity usually >340 mOsm/L
• ▪ 
  Serum Na ⁺ : may be ↓, nl, or ↑; if nl or ↑, the pt is severely dehydrated because glucose draws fluid from intracellular space = ↓ serum Na ⁺ ; the corrected Na ⁺ can be obtained by the serum Na ⁺ concentration by ↑ 1.6 mEq/dL for every 100 mg/dL ↓ in the serum glucose level above nl.
• ▪ 
  Serum K ⁺ : may be ↓, nl, or ↑; regardless of the initial serum level, the total body deficit is approximately 5 to 15 mEq/kg.
• ▪ 
  Serum bicarbonate: usually >12 mEq/L (average is 17 mEq/L)
• ▪ 
  Arterial pH: usually >7.2 (average is 7.26). Both serum bicarbonate and arterial pH may be lower if lactic acidosis is present.
• ▪ 
  ↑ BUN: Azotemia (prerenal) is usually present (BUN generally ranges from 60-90 mg/dL).
• ▪ 
  ↓ PO ₄ ^-3 : hypophosphatemia (average deficit is 70-140 mM)
• ▪ 
  ↓ Ca ²⁺ : hypocalcemia (average deficit is 50-100 mEq)
• ▪ 
  ↓ Mg ²⁺ : hypomagnesemia (average deficit is 50-100 mEq)
• ▪ 
  CBC w/diff, U/A, blood and urine cultures should be performed to r/o infectious etiology.

Treatment

• ▪ 
  Vigorous IV fluid replacement, electrolyte replacement, insulin Rx (see Fig. 5-1 )

B

Hypoglycemia

Definition

Hypoglycemia can be arbitrarily defined as a plasma glucose level <50 mg/dL. To establish the dx, the following 3 criteria are necessary:

• ▪ 
  Presence of sx
  • • 
    Adrenergic: sweating, anxiety, tremors, tachycardia, palpitations
  • • 
    Neuroglycopenic: seizures, fatigue, syncope, headache, behavior changes, visual disturbances, hemiplegia
• ▪ 
  ↓ Plasma glucose level in symptomatic pt
• ▪ 
  Relief of sx after ingestion of carbohydrates

Etiology

• ▪ 
  Reactive hypoglycemia
  • • 
    Hypoglycemia usually occurs 2 to 4 hr after a meal rich in carbohydrates.
  • • 
    These pts never have sx in the fasting state and rarely experience loss of consciousness secondary to their hypoglycemia.
  • • 
    Pts who have had subtotal gastrectomy rapidly absorb carbohydrates. This causes an early plasma glucose level followed by a late insulin surge that reaches its peak when most of the glucose has been absorbed and that results in hypoglycemia.
  • • 
    Pts with type 2 (non–insulin-dependent) diabetes can experience hypoglycemia 3 to 4 hr postprandially secondary to a delayed and prolonged second phase of insulin secretion.
  • • 
    Congenital deficiencies of enzymes necessary for carbohydrate metabolism and functional (idiopathic) hypoglycemia are additional causes of reactive hypoglycemia.
• ▪ 
  Fasting hypoglycemia
  • • 
    Sx usually appear in the absence of food intake (at night or during early morning).
  • • 
    Etiology: insulinoma, mesenchymal tumors that synthesize insulin-like hormones, adrenal failure, glycogen storage disorders, severe liver disease or renal disease
• ▪ 
  Iatrogenic or drug-induced: hypoglycemic drugs, excessive insulin replacement, factitious, ethanol-induced hypoglycemia

Diagnosis

• ▪ 
  When the plasma glucose level is ↓ (e.g., fasting state), the plasma insulin level should also be ↓. Any pt presenting w/fasting hypoglycemia of unexplained cause should have the following tests drawn during the hypoglycemic episode ( Table 5-5 ):
  • • 
    Plasma glucose
  • • 
    Plasma insulin level
  • • 
    Plasma C-peptide
  • • 
    Plasma and urine metabolites of sulfonylurea levels and meglitinides
  TABLE 5-5

  Hypoglycemia in Nondiabetic Pt. Laboratory Differentiation of Factitious Hypoglycemia and Insulinoma

  Lab	Insulinoma	Exogenous Insulin	Oral Hypoglycemic Agents (Sulfonylurea/Meglitinides)
  Plasma glucose	↓	↓	↓
  Serum insulin	↑	↑↑	↑
  Plasma and urine sulfonylureas/meglitinides	Absent	Absent	Present
  C-peptide	↑	N/↓	↑
• ▪ 
  Factitious hypoglycemia should be considered, especially if the pt has ready access to insulin or oral hypoglycemic agents (e.g., medical or paramedical personnel, family members who are diabetic or in the medical profession).
• ▪ 
  Pancreatic islet cell neoplasms (insulinomas) are usually small (<3 cm), single, insulin-producing adenomas. Measurement of inappropriately serum insulin levels despite ↓ plasma glucose level after prolonged fasting (24-72 ↑ hr) is pathognomonic of these neoplasms.

Treatment

• ▪ 
  Variable, depending on etiology of hypoglycemia