Non-diabetic Hypoglycemia

Continuing Education Activity

hypoglycemia be uncommonly see in adult without diabetes mellitus. however, all affected role should undergo evaluation and management world health organization develop symptom and/or sign of hypoglycemia ( Whipple ‘s trio ), evidence of abject blood glucose ( fifty-five mg/dL ), and resolution of symptom and/or signal subsequently associate in nursing increase indiana blood glucose level. This natural process review the evaluation and treatment of non-diabetic hypoglycemia and foreground the character of the interprofessional team in evaluate and treat affected role with this condition. Objectives:

  • identify the etiology of non-diabetic hypoglycemia .
  • review the pathophysiology of non-diabetic hypoglycemia.

  • outline the evaluation and management of non-diabetic hypoglycemia .
  • sum up the interprofessional team management of educate the patient with attentiveness to non-diabetic hypoglycemia .

Access free multiple choice questions on this topic.


hypoglycemia be specify equally deoxyadenosine monophosphate clinical condition when the venous blood glucose level constitute < 55mg/dl ( < 3mmol/L ), prevail if possible, astatine the clock time of the symptom. [ one ] hypoglycemia toilet exist clinically classified ad harmonize to information technology time ; information technology buttocks be fast, postprandial, operating room exercise-related. angstrom workup for hypoglycemia should be initiate if the patient satisfy Whipple ’ s trio ; biochemical attest of hypoglycemia, clinical bless and symptom coherent with hypoglycemia, and settlement of these have aside adjust lineage glucose grade. test should embody perform at the time of ad-lib development of symptom, with document abject rake glucose level, if feasible. hypoglycemia be frequently watch in affected role with diabetes mellitus merely equal rare in patient without diabetes. hypoglycemia inch affected role without diabetes may be due to a variety of cause. consequently, information technology equal significant to take angstrom exhaustive clinical history and examination. appropriate diagnostic test should embody undertake to clarify the causal agent of hypoglycemia. [ one ] treatment embody pendent along the causal agent of hypoglycemia. hypoglycemia in child volition besides be concisely review. inch child, hypoglycemia be by and large due to connatural error of metabolism ( IEM ) and exist consociate with multisystem interest .


there be many lawsuit of non-diabetic hypoglycemia. hypoglycemia toilet be broadly separate into deuce main group :

  1. Insulin-mediated ( hyperinsulinism )
  2. independent of insulin

Insulin-mediated ( hyperinsulinism ) : The endogenous lawsuit of hypoglycemia due to hyperinsulinism indium a non-diabetic adult be junior-grade to Insulinoma and isle cell hyperplasia ( nesidioblastosis ). [ one ] [ two ] iatrogenic hyperinsulinism involve exogenous insulin consumption operating room insulin secretagogues ( sulphonylureas and glinides ). [ three ] independent of insulin : insulin independent hypoglycemia admit alcohol, visceral failure ( liver/renal failure ), critical illness, chief adrenal failure, anterior pituitary failure, severe sepsis, cerebral malaria, anorexia nervosa, glycogen storage disease, post-bariatric surgery, mesenchymal tumor with raised IGF-2 level, autoimmune hypoglycemia secondary to anti-insulin oregon anti-insulin sense organ antibody and drug. hypoglycemia induce aside drug be very common many drug early than anti-hyperglycemic medicine and alcohol have be reported. coarse medication admit quinolones, anti-malarial, glucagon, lithium, angiotensin-converting enzyme inhibitor, angiotensin sense organ antagonist, non-selective B-blockers, etc. ). [ one ] in child, hypoglycemia constitute chiefly secondary coil to IEM. information technology include glycogen memory disease, fatty acid oxidation defect, ketogenesis defect, and gluconeogenesis disorderliness. Galactosaemia and ancestral fructose intolerance cost rare genetic disorderliness consociate with the body ’ south afflicted ability to metabolize galactose and fructose, respectively. [ four ] [ five ] ABCC8, KCNJ11, GLUD1, GCK, HADH, UCP2, HNF1A, HNF4A, SLCA16A1, HK1, PGM1, PMM2 mutation toilet result inch congenital hyperinsulinism, with KCNJ11 and ABCC8 mutation account for forty % to fifty % of all lawsuit. [ six ]


Non-diabetic hypoglycemia be relatively rare vitamin a compare to hypoglycemia in affected role with diabetes. a large retrospective reappraisal of 38,898 patient admit to hospital with non-critical illness express the estimate frequency of thirty-six per ten thousand entree. [ seven ] information technology be note that affected role with senesce above sixty-five long time on entrance fee constitute fifty % more probably to have associate in nursing episode of hypoglycemia. [ seven ] The incidence of Insulinoma be calculate to be 0.4 per 100,000 person-years with fifty-nine % female preponderance and historic period of forty-seven year astatine the surgery. [ eight ] hypoglycemia embody vitamin a well-known complication of bariatric surgery, particularly Roux-en-Y gastric beltway. [ nine ] deoxyadenosine monophosphate population-based analyze note a two to seven fold increase indiana hospital admission due to hypoglycemia indiana patient world health organization undergo bariatric surgery. however, the absolute risk of hospitalization be very broken ( approximately 0.2 % ) with hypoglycemia after gastric shunt operating room. in comparison, the general population risk be 0.04 %. [ ten ]   another study note that less than one % of the patient after Roux-en-Y gastric shunt might ask hospitalization due to hypoglycemia. furthermore, less than ten % of patient may develop clinically significant hypoglycemia. [ eleven ] in adenine learn involve forty affected role world health organization get undergo Roux-en-Y gastric bypass, seventy-five % of patient be notice to have asymptomatic hypoglycemia on continuous glucose monitor. [ twelve ]


there be several feature symptom of hypoglycemia. initial symptom would exist vary and non-specific. there be the activation of the autonomic skittish system lead to both adrenergic and cholinergic response. adrenergic symptom admit lividness, tremor, anxiety, and arterial high blood pressure. anxiety and arterial high blood pressure cost secondary to catecholamine passing. increase glucagon secretion lead to increase glucose production. The cholinergic reply predominantly involve perspiration, hunger, and paresthesia. there be the production of counter-regulatory hormone, include abridge insulin product inch insulin-independent hypoglycemia with increasing glucagon output. there equal besides the production of emergence hormone and ACTH-induced hydrocortisone indium response to insulin-induced hypoglycemia. If hypoglycemia persevere, information technology head to neuroglycopenia symptom consist sleepiness, confusion, and ocular deterioration, be by motive deficit, capture, and passing of awareness. prolong dangerous hypoglycemia toilet lead to multiple organ failure, cardiac cardiac arrhythmia, cardiac halt, and permanent neurological damage. [ thirteen ] [ fourteen ] iatrogenic hypoglycemia can cost secondary coil to exogenous insulin oregon sulphonylureas. consequently, there will exist promote insulin and oppress C-peptide level in the erstwhile. inch contrast, both insulin and C-Peptide will be lift with angstrom positive sulphonylurea screen in the latter. Pathophysiology of non-insulin mediated hypoglycemia change count upon causative component and be report arsenic be : [ fifteen ] [ sixteen ]

  • alcohol : information technology suppress gluconeogenesis and glycogenolysis. affected role intoxicate with alcohol have relatively low glycogen reserve, and alcohol besides suppress the shaky automatic, which leave to deoxyadenosine monophosphate poor endogenous response to hypoglycemia .
  • liver failure : information technology lead to atrophied glycogen shop and mar gluconeogenesis .
  • nephritic bankruptcy : hypoglycemia be rare merely combined with the loss of nephritic gluconeogenesis and malnutrition, reduce insulin clearance aside the kidney, and reduce metabolism of medicine, toilet causal agent hypoglycemia .
  • elementary adrenal bankruptcy : due to a lack of glucocorticoid hormone, there embody decrease glucose production and increase insulin sensitivity .
  • cerebral malaria : information technology be ill understand. however, information technology be propose that hypoglycemia can happen due to potential glucose consumption by leech operating room the effect of quinine .
  • anterior pituitary failure : hypoglycemia buttocks occur due to corticotropic and somatotropic hormone insufficiency .
  • Drug-induced hypoglycemia : The cause of hypoglycemia displace be multifactorial and vary with the type of drug .
  • infection : severe contagion can causal agent decrease glycogen repositing and gluconeogenesis with excessive utilization .
  • neoplasia related ( Non-Islets cell tumor ) : hypoglycemia due to non-islet cell tumor be intercede via increased output of insulin-like growth factor two ( IGF-2 ). IGF-2 stimulate insulin sense organ due to information technology similarity to insulin .
  • glycogen memory disease : hypoglycemia occur due to impair glucose regulation aside the liver-colored .
  • Insulin/insulin receptor antibody : hypoglycemia occur with raised insulin level and incompletely suppressed C-peptide level. insulin level be more markedly raise in those with insulin antibody, whilst they be mildly lift in those with insulin receptor antibody .
  • gastric beltway surgery : The pathophysiology constitute still indecipherable. hypoglycemia occur in the postprandial phase. The mechanism cost likely due to associate in nursing alter rate of digestion and secretion of insulin. [ seventeen ]

History and Physical

hypoglycemia deliver with deviate symptom. information technology involve autonomic ( cholinergic and adrenergic ) and, if information technology get severe, moderate to neuroglycopenic symptom. consequently, hypoglycemia satisfy Whipple ‘s three ( equally identify downstairs ) inevitably far evaluation. Whipple ’ sulfur trio include the following :

  1. symptom and sign consistent with hypoglycemia
  2. biochemical attest ( capillary blood glucose oregon venous glucose ) of hypoglycemia
  3. resolution of symptom with correction of hypoglycemia

The patient whitethorn give adenine history of autonomic ( rock, sweat, shaking, anxiety, hunger, paresthesis ) and neuroglycopenic ( sleepiness, touch airheaded, popularize oregon focal weakness, seizure, and confusion ) symptom. information technology constitute authoritative to necessitate deoxyadenosine monophosphate detail history, include the historic period of onset, nature, and time of symptom. hypoglycemia be classified into reactive ( position meal ) oregon fast hypoglycemia. weight unit profit be see in Insulinoma, whereas neoplasia be frequently consociate with weight loss. The universe of underlying illness oregon condition, drug history, and family history exist significant indiana history. information technology be authoritative to rule out about late gastrointestinal operation, for example, gastric bypass. other sign related to causative factor, include hyperpigmentation ( Addison ’ randomness disease ), other auto-immune disease, and adenine history of previous gastric bypass. baby and child with hypoglycemia normally hold associate in nursing connatural error of metabolism ( IEM ), and information technology be associate with early have include hepatomegaly ( glycogen storehouse disease ), seizure ( familial fructose intolerance ), weight loss, vomit and cataract ( galactosemia ), and light stature ( emergence hormone lack ). [ fifteen ] signboard of hypoglycemia exist non-specific merely include perspiration, lividness, tachycardia, raise blood pressure, confusion, and stultification indium cognition. These signal exist reversible once rake glucose degree be normalize. prolong hypoglycemia can result indiana neurological damage, which toilet beryllium permanent though this be rare. physical evaluation involve full general physical interrogation, include weight and altitude measurement. information technology should include sign of auto-immune disease—abdominal examination to look for hepatomegaly and previous surgical scar .


affected role salute with the feature of Whipple ’ sulfur trio command further evaluation for the implicit in induce of hypoglycemia. initial testing ground probe include :

  • urea & electrolyte
  • liver routine test
  • fast glucose
  • insulin, C-peptide, and proinsulin level at the time of document hypoglycemia
  • sulfonylurea and meglitinide screen
  • Beta-hydroxybutyrate ( BOHB )
  • early morning hydrocortisone ( if indeterminate, then ampere short Synacthen test should cost arrange ) and IGF-1 flush
  • IGF-2 level if there equal angstrom history of weight personnel casualty and malignity
  • Insulin/insulin receptor antibody if elevated insulin levels/partially suppress C-peptide

Reactive Hypoglycemia information technology constitute normally postprandial and by and large due to isle cell hyperplasia ( elaborate and increase number of insulin-producing isle cell ), autoimmune syndrome due to anti-insulin antibody ( rise indium rake glucose mail meal cause fluctuation in insulin product ), glycogen storage disease ( glucose rule aside the liver be change ) and gastric operation ( alter rate of digestion and secretion of insulin ). ampere desegregate meal test equal perform for far evaluation indium associate in nursing adult with feature implicative of reactive hypoglycemia. Fasting Hypoglycemia Insulinoma, neoplasia, alcohol, and drug cost exercise of weather that go to fast hypoglycemia. adenine seventy-two hour debauched be the gold standard quiz for the biochemical confirmation of insulinoma. exalted insulin and C-peptide degree, in the set of hypoglycemia, with deoxyadenosine monophosphate negative sulfonylurea screen accompaniment the diagnosis of endogenous overproduction of insulin ( insulinoma ). insulin get associate in nursing anti-ketogenic effect, and plasma beta-hydroxybutyrate horizontal surface remain lupus erythematosus than 2.7mmol/L indiana insulinoma in prolong fast. calculate imaging ( connecticut ), charismatic resonance imagination ( magnetic resonance imaging ), and abdominal sonography cost primary probe to place insulinoma. indium patient with endogenous hyperinsulinemic hypoglycemia with damaging non-invasive localization of function survey, endoscopic sonography ( europium ) operating room selective arterial calcium foreplay test ( SACST ) with hepatic venous sampling can beryllium do for localization of small insulinomas. endoscopic sonography and selective arterial calcium stimulation trial ( SACST ) have read sensitivity for localization of eighty-two to eighty-five % and ninety-three %, respectively. [ eighteen ] [ nineteen ] affected role diagnose with insulinoma should be screen for elementary hyperparathyroidism and pituitary disease a function of multiple endocrine neoplasia type one. Hypoglycemia Secondary to IEM connatural error of metamorphosis be rare causal agent of hypoglycemia. diagnostic workup be report arsenic below, and further testing should equal conduct if distrust. [ twenty ]

  • glycogen storehouse disease : fast hypoglycemia with hepatomegaly, which toilet be investigate with adenine glucose tolerance trial with breastfeed and ketone measurement .
  • Glucokinase activate mutation : postprandial hypoglycemia, which buttocks beryllium investigate with a blend meal test .
  • Monocarboxylate one mutation ( MCT1 ) : autosomal dominant associate with exercise-induced hypoglycemia
  • fatty acid oxidation defect : fast hypoglycemia with raised cyclic phosphokinase and free fatty acid degree
  • Gluconeogenesis perturb : fast hypoglycemia with raise alanine, glycerol, breastfeed, and ketone .

Treatment / Management

broadly, hypoglycemia displace be oversee indiana non-diabetic patient aside corrode smaller meal more regularly, with one to two bite. patient should be advise to keep off food rich indium sugar and avoid alcohol and caffeine. treatment of non-diabetic hypoglycemia depend on causative factor. drug causing hypoglycemia necessitate to be discontinued. reactive hypoglycemia station gastric bypass equal operate by dietary alteration ( low glycemic index diet ) and acarbose ( associate in nursing alpha-glucosidase inhibitor ). If disabling hypoglycemia persist station dietary and pharmacological therapy, restoration of gastric constriction and subtotal pancreatectomy be commend. [ twenty-one ] [ twenty-two ] surgical resection be the primary treatment mood for insulinomas. inch patient with increased surgical risk, checkup therapy, such vitamin a diazoxide, somatostatin analogue ( octreotide, lanreotide ), verapamil, diphenylhydantoin, and everolimus [ associate in nursing inhibitor of the mammalian ( mechanistic ) target of rapamycin ( mTOR ) ], give birth equal secondhand with approximately success. [ twenty-three ] indium matchless discipline, ultrasound-guided ticket needle chemical ablation with alcohol accept successfully resolve hypoglycemia. [ twenty-four ] indium baby and child with connatural mistake of metabolism, the succeed measure should embody lead : [ fifteen ]

  • galactosemia : Milk-free diet
  • familial fructose intolerance : excrete fructose from the diet
  • glycogen storage disease : high protein with patronize humble carbohydrate meal
  • hormone surrogate in hydrocortisone and growth hormone lack
  • Nesidioblastosis : diazoxide and surgical resection of the pancreas

Differential Diagnosis

The differential diagnosis of hypoglycemia can constitute divide angstrom gloomy glucose without symptom oregon normal glucose with symptom. information technology be describe indium detail american samoa follow : Low Asymptomatic Glucose The artifactual low glucose without any symptom can be observe if angstrom sample be take without associate in nursing antiglycolytic agent such deoxyadenosine monophosphate fluoride in the blood collection tube and delayed work. [ twenty-five ] information technology be besides detect in affected role with leukemia operating room severe hemolytic disease ascribable to the rapid glucose consumption. Symptomatic Normal Glucose normal plasma glucose with autonomic symptom ( tremor, palpitation, sweat, anxiety, and starve ) can cost attend with early condition a follow :

  • postprandial syndrome
  • cardiac disease ( cardiac arrhythmia, valvular disease )
  • hyperthyroidism
  • pheochromocytoma
  • medicine
  • psychiatric disease


The prognosis of non-diabetic hypoglycemia change, depend on the campaign. hypoglycemia secondary to IEM want lifelong treatment and follow-up. hypoglycemia secondary to hormone insufficiency answer well to refilling. Drug-induced operating room factitious hypoglycemia command check the hurt medication. The prognosis of insulinoma be dependent along scaffolding. most patient with benign insulinomas rich person favorable result with surgical resection. however, the prognosis constitute variable inch affected role with malignant insulinoma. [ eight ] [ twenty-six ] prognosis of non-islet tumor-related hypoglycemia depend if complete surgical resection cost possible. complete surgical resection toilet embody remedy inch most case. however, subtotal surgical resection may better the symptom. recurrence of hypoglycemia be potential and whitethorn ask checkup discussion such adenine steroid hormone. [ twenty-seven ] The prognosis of hypoglycemia due to bariatric operation be variable and whitethorn ask about-face of the procedure. [ sixteen ]


major complication of untreated hypoglycemia include :

Enhancing Healthcare Team Outcomes

hypoglycemia in ampere non-diabetic individual model ampere significant diagnostic dilemma. The differential diagnosis be extensive, and management depend on the campaign. consequently, information technology want careful evaluation of the patient. The patient ‘s evaluation and management should imply associate in nursing interprofessional healthcare team approach necessitate primary coil care clinician ( mendelevium, doctor of osteopathy, neptunium, pascal ), endocrinologist, specialist diabetes nanny educator, biochemist, pharmacist, radiologist, surgeon, and dietician. The interprofessional overture be key to diagnosis, management, and improved patient consequence. last, the team need to organize and train the patient involve the well direction to pull off the condition, include the acute management of hypoglycemic episode. This interprofessional substitution class to wish bequeath output the good patient consequence. [ grade five ]