Non-emergent new onset, symptomatic, severe hyperglycemia


Medical Student Clinical Pearl – September 2020


Nick Quinn

Year: 4
DMNB Class of 2021

Reviewed and Edited by Dr. Stephen Hull (Endocrinologist) and Dr. David Lewis


All case histories are illustrative and not based on any individual


Case Report

A 64-year-old man present to the ED after noting a random blood glucose of 32 while at his daughter’s house that he checked with her point of care glucose monitoring. He reports a 6-week history of polyuria, polydipsia, and 15-pound weight loss over the past 4 weeks. He also reports refractory oral candidiasis infection for which he had seen his primary care provider about.

His past medical history is significant for only hypertension and benign prostatic hyperplasia, for which he takes hydrochlorothiazide and tamsulosin.

On exam, he is a mildly obese man with abdominal adiposity, he appears well but anxious, he is in no physical distress. He is alert, and oriented to person, place, and time, although at times seems mildly tangential. There is no jaundice, he is not diaphoretic, he appears to be perfusing well.

His GCS is 15, his heart rate 92 and regular, blood pressure is 116/72, his respiratory rate is 18, temperature is 36.8 degrees, and his oxygen saturation is 96% on room air, his glucose was 46 mmol/L.

His cardiac and respiratory exam are unremarkable. His abdomen is scaphoid, soft, non-tender, there is no guarding, rigidity, rebound tenderness, there are no masses felt, or signs of extra hepatic manifestations of liver disease. A fluid status exam reveals dry mucous membranes, dry axilla, normal skin turgor, and a normal capillary refill. In addition to a dry oropharynx, there is also leukoplakia present. His pupils are equal and reactive to light bilaterally, his strength and sensation is normal bilaterally in both his upper and lower limbs, there is no tremor present.


Initial Assessment

Initial survey of someone presenting with symptomatic hyperglycemia should be to rule out diabetic ketoacidosis (DKA), which occurs more commonly, though not exclusively in patients with type 1 diabetes, and hyperglycemia hyperosmolar state (HHS), which again occurs more commonly though not exclusively in patients with type 2 diabetes, both of which can be serious acute complications from diabetes and can cause a patient to become unstable. Initial primary survey should include an assessment to exclude precipitating causes of hyperglycemia including the I’s of DKA and HHS[1]:


  • Insulin deficiency (new onset T1DM, failure to take enough insulin)
  • Infection (PNA and UTI)
  • Ischemia or infarction (MI, CVA, Acute mesenteric ischemia)
  • Inflammation (pancreatitis, cholecystitis)
  • Intoxication (Alcohol, drugs)
  • Iatrogenesis (glucocorticoids, thiazides)

Despite the age of this symptomatic, severe hyperglycemic patient, late onset type 1 diabetes should remain on the differential. As such, a pertinent family history should be elucidated, which includes type 1 or type 2 diabetes, the age of diagnosis, and history of other autoimmune conditions. Similarly, noting the presence or absence of other markers of insulin resistance or metabolic syndrome are helpful to determine a diagnosis which would be more in keeping with a diagnosis of type 2 diabetes. Some of the signs of insulin resistance include:

  • Impaired glucose tolerance, impaired fasting glucose
  • Coronary artery disease
  • Metabolic syndrome (abdominal adiposity, low HDL, hypertriglyceridemia, hypertension, impaired fasting glucose)
  • Polycystic ovarian syndrome
  • Non-alcoholic fatty liver disease
  • Acanthosis nigricans


Classic presentation of hyperglycemia:

Most patients with hyperglycemia will be asymptomatic if their plasma glucose is in the mild range, however once plasma glucose rise above the renal threshold, patients can develop an osmotic diuresis, which can lead to the classic presentation of[1]:

  • Polyuria
  • Polydipsia
  • Polyphagia
  • Weight loss


The subsequent diuresis and dehydration may lead to a variety of other symptoms as well including tachycardia, lightheadedness, and weakness as a result of possible electrolyte abnormalities. As the degree of hyperglycemia worsens, subsequent dehydration and electrolyte abnormalities secondary to the osmotic diuresis may lead to additional symptoms including[2]:


  • Abdominal pain
  • Tachypnea (or Kussmaul’s respirations with acidosis)
  • Hypotension
  • Ketotic breath (fruity odor)
  • Marked tachycardia
  • Neurologic symptoms (seizures, focal weakness, lethargy, coma, death)


Acute Metabolic Decompensation Spectrum of Diabetes

Although occasionally understood as discrete entities, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are conditions that exist at either ends of a spectrum of acute metabolic decompensation of diabetes that share a similar pathophysiology [3]. Both conditions are characterised by a decreased net effect of insulin, with concomitant dysregulation of certain hormones, including glucagon, catecholamines, and cortisol, as well as significant dehydration and electrolyte abnormalities [3]. At one end, DKA is characterized by complete lack of insulin due to absent pancreatic secretions or exogenous insulin, and results in acidosis and ketosis but lacks hyperosmolarity; at the other end, HHS is characterized by a hyperosmolar state without acidosis[4]. To appreciate these two mechanisms and their spectrum, it’s important to first understand the pathogenesis of type 1 and type 2 diabetes.


Type 1 diabetes is an autoimmune disease whereby the immune system produces autoantibodies against pancreatic beta cells, leading to their eventual destruction, and complete absence in the capacity for insulin production. As such, without exogenous administration of insulin and subsequent uptake of glucose by the cells, glucagon is secreted which results in increased gluconeogenesis and glycogenolysis [5]. The increased concentration of glucose in the blood results in a process of osmotic diuresis and eventual significant dehydration through loss of water and electrolytes [3]. Similarly, without insulin present for glucose uptake by cells, the process of lipolysis increases to form free fatty acids as a compensatory mechanism for energy production. These free fatty acids are taken up by the liver and formed into ketones to be used as an energy source. However, due to their low pKa, ketones cause the blood to become more acidic [4]. Attempts are made to buffer the ketoacidosis with hyperventilation, but it is eventually overwhelmed resulting in metabolic decompensation and metabolic acidosis – the resulting state is known as DKA[4].


The development of Types 2 diabetes occurs over a prolonged period of time which initially begins with insulin resistance, whereby the glucose transporters are less sensitive to insulin, and it becomes more difficult for glucose to enter the cell. Initially, the pancreas compensates by increasing insulin secretion to maintain normal levels of glucose uptake [5]. However, eventually, the pancreas is not able to meet the demands of the increasing insulin resistance, and blood glucose levels begin to rise – it is at this point where the pancreas beta cell mass begins to decline as it is no longer able to sustain the elevated levels of insulin production [5]. As this process continues, the pancreas beta cells are no longer able to compensate, and rapid rises in glucose will be seen. Eventually, this process will lead to severe reduction in beta cell mass and significant reductions in the capacity to produce insulin, leading to type 2 diabetes [5]. Because there is typically some degree of beta cell function maintained, the process of ketosis is typically avoided in acute situations that may precipitate metabolic decompensation [3]. The presence of some insulin inhibits the process of increased lipolysis and subsequent production of acid-promoting ketone bodies for energy sources during these acute metabolic decompensation scenarios. Nonetheless, the relative deficiency in insulin results in significant increases in blood glucose, which ultimately leads to both a hyperosmolar state as well as an osmotic diuresis and significant levels of dehydration, known as hyperglycemic hyperosmolar state[5].


Through this illustration of either complete or relative insulin deficiency and the resulting metabolic decompensation, it can be seen how physiologic characteristics between these extremes could be observed. Depending on the proportion of beta cell mass and function that is preserved, different levels of insulin secretion could be observed, resulting in a continuum between hyperglycemic ketoacidosis and hyperosmolar hyperglycemic states.



Initial investigations of symptomatic hyperglycemia should include a basic metabolic profile, CBC, venous blood gas, additional electrolytes (for those who may be suspected of profound dehydration), ECG (acidemia may result in extracellular potassium shifts and demonstrate ECG changes consistent with hyperkalemia), and a urinalysis with culture and sensitivity[6].


Case Continued…

His plasma glucose was 43 mmol/L, his CBC was normal, his Na was 132, his K+ was 3.8, his Cl was 109 mmol/L, his BUN was 6 mmol/L, and his creatinine was 98 mmol/L. His serum osmolality was 294 mmol/L. Urine dipstick was negative for signs of infection, negative for ketones, and positive for glucose. The venous blood gas revealed a pH of 7.41, pCO2 of 43, his bicarb was 26. His ECG was normal sinus rhythm.

At this point, the working diagnosis was new onset type 2 diabetes with symptomatic severe hyperglycemia and mild dehydration. He did not have any significant alteration in his mental status nor did his serum osmolality meet criteria for hyperosmolar hyperglycemic state diagnosis – it was elevated, but not significantly. No precipitating event was identified.



Management for DKA and HHS is centered around correcting intravascular volume depletion, correcting electrolyte abnormalities, and insulin replacement therapy. Many recommendations and protocols exist for individuals who present in DKA or HHS, however management and disposition of symptomatic, severe hyperglycemia is less clear from the emergency department perspective[8].

Due to the dehydration, intravenous normal saline (0.9%) for the first few hours is often used for fluid management in HHS, and then switching to ½ NS once the serum sodium normalizes [2]. Unless the patient is truly volume deplete, he may not require intravenous fluid resuscitation in this scenario and oral intake is likely adequate.

For symptomatic (catabolic – polydipsia, polyuria, unintentional weight loss) insulin is recommended as the initial treatment modality in all individuals, rather than an oral hypoglycemic agent such as metformin[2]. After insulin has been initiated, and if plasma glucose is well controlled in the near term, it may be possible to discontinue insulin therapy for some individuals and transition to oral hypoglycemic agents, however this decision would require careful follow-up and the involvement of either endocrinologists or general internists.

Insulin administration may be through subcutaneous injections, or through an intravenous line, depending on the severity of hyperglycemia. IV insulin infusion may be appropriate for DKA or HHS, however in the present case, starting a subcutaneous injection as part of a home insulin regimen while admitted or upon discharge would be appropriate, as starting an insulin infusion may delay discharge from hospital. Often, a plasma glucose target for hyperglycemia before discharge from the ED that would be appropriate is 20 mmol/L[8].

Once the plasma glucose has been normalized, the patient needs to continue on a diabetes management plan. It would be appropriate to involve endocrinologists or general internists for decisions in both the acute management as well as to plan follow up management. These specialists would be able to advise on some of the topics discussed above including diagnosis, treatment, management of complications, decisions on insulin administration, discussions with patients regarding the implications of their new diagnosis including lifestyle interventions, decisions around hypoglycemic agents, costs, recommended screening for complications, associated risks, among others. Similarly, the endocrinologist can recommend and facilitate the referral to a diabetes educator.

The Canadian Diabetes Association recommends a multifaceted treatment plans for newly diagnosed diabetes, including diabetes education, healthy behaviour intervention, and screening for complications[9]. A diabetes educator, along with other healthcare providers, can coordinate self-management education (SME). SME is defined as a systematic intervention that involves active participation by the individual in self–monitoring of health parameters and/or decision-making with the application of knowledge and skills acquired during education sessions[10]. There is a strong body of literature which suggests educational interventions that emphasize knowledge, emotional and behaviour support, coping strategies and self-management training can promote improved glycemic control at all ages[11]. Similarly, there is strong evidence to suggest that SME is associated with important clinical outcomes in people with diabetes including reductions in A1C levels, improvements in cardiovascular risk factors, and reductions in foot ulcerations, infections and amputations [11].

The Canadian Diabetes Association also recommend that anyone with evidence of metabolic decompensation (marked hyperglycemia, ketosis, or unintentional weight loss) and/or symptomatic hyperglycemia should be started immediately on a home insulin regime, regardless of A1C level [9].

Home insulin regimens

For an individual being discharged with a new diagnosis of type 2 diabetes, who was not previously on any antihyperglycemic agents, and has an indication for initiation of insulin such as the present case, an appropriate strategy would be to initiate either

  1. Basal insulin (with or without metformin)– 10 units of basal insulin at bedtime
  2. Basal-bolus – total daily dose of 0.3 to 0.5 units/kg; 40% of total daily dose as basal insulin, and 20% of total daily dose as bolus insulin 3 times per day using rapid-acting insulin[9].

For both approaches, patients can either self-titrate to a target fasting glucose of 4.0 to 7.0 mmol/L (or individualized target), or titration may be done in conjunction with a healthcare provider [9]. For self-titration, patients adjust their bedtime basal insulin by 1 unit every day until at target [9]. However, if using the ultra-long-acting basal insulins such as degludec, patients should adjust by 2 units every 3-4 days, or 4 units once a week until target is reached.

Lantus Dosing Calculator

Diabetes Canada – Insulin Prescription


Discharging a patient on a new insulin regimen raises concerns for either non-adherence, improper dosing, and hypoglycemia. Despite not being in HHS or DKA, the new onset symptomatic severe hyperglycemia patient may require a brief admission to hospital if the risk of an adverse event occurring upon discharge is significant.


Discharge from the hospital with a new prescription for Insulin – The Evidence

One study from Chicago used an emergency department rapid acting protocol to determine if it would have an impact on degree of hyperglycemia, ED length of stay, and adverse events including hypoglycemia. They were trying to achieve the American Diabetes Association recommendation target blood glucose level of <10 mmol/L before discharge to expedite discharge from the ED[12]. They demonstrated the more aggressive ED protocol with rapid acting insulin did result in better glycemic control by an additional 5 mmol/L and a 36 hour reduction in hospital length of stay, but it did not affect ED length of stay[12]. The rate of hypoglycemia was 7.4%, suggesting the aggressive insulin protocol is not without risk and hypoglycemia should be considered as a potential risk when discharging someone on insulin for new onset diabetes[12].

Another study looked at the association between plasma glucose levels at time of discharge from the ED and 7-day adverse events including DKA/HHS, repeat ED visits, or admission to hospital amongst patients who had originally presented to ED with at least a plasma glucose level of 22 mmol/L. The found rates of return visits for hyperglycemia was 13%, hospitalization was 7%, and that of iatrogenic hypoglycemia was 2%[13]. They also concluded that an elevated discharge glucose level was not associated with increased risk of repeat ED visits or hospitalization within 7 days, and suggested the ED management should be focused on ensuring appropriate outpatient follow-up and treatment of long-term glycemic control instead of aiming for a “safe” glucose threshold before discharge[13]. A Canadian study trying to determine risk factors for repeat ED visits in patients presenting with hyperglycemia from any cause found that being on insulin was associated with an increased risk for repeat ED visits (OR 1.9) again supporting the idea that insulin regimens do pose a risk for complications and subsequent repeat ED visits[14].


Back to the case…

Generally, patients with HHS or DKA are admitted to hospital, however there are no recommendations for the symptomatic severe hyperglycemic patient and should be determined by a thorough clinical evaluation. When deciding the disposition for this type of patient, several important factors should be considered when deciding whether or not to discharge someone on insulin: the level of social support system at home; any informal care that could be provided through friends or family; his overall general capacity to adhere to the insulin regimen; whether or not he has a family doctor; his relative health literacy; and his socioeconomic status. Depending on these factors, someone may be at a high risk for hypoglycemia, HHS, or other metabolic derangements if they are unable to adhere to the insulin regimen.

The patient in the ED was felt to have a relatively low level of health literacy, and he lived on his own, and was of a lower SES. He had few other medical comorbidities and had difficulty understanding his current presentation, which we felt decreased his ability to manage his new onset type 2 diabetes with an insulin regimen. As such, the patient was consulted to family medicine and subsequently admitted to hospital where he could then be monitored and subsequently enrolled in the diabetes education program to receive adequate information on his new diagnosis and management approach. He was also started on an insulin infusion given his plasma glucose level of 43 mmol/L. Alternatively, if they patient was determined to be of low risk for HHS or hypoglycemia or other metabolic derangements from non-compliance, they could be discharged home on insulin and then instructed to follow-up with both their family doctor and attend the next diabetes education program[9].



  • DKA and HHS must be ruled out in the symptomatic hyperglycemic patient in the emergency department
  • DKA and HHS exist on a spectrum of acute metabolic decompensation complication of diabetes
  • Individuals with new onset symptomatic severe hyperglycemia consistent with type 2 diabetes should be started on insulin therapy
  • Consultation of endocrinology and diabetes education are critical components for the assessment and management plan for new onset symptomatic severe hyperglycemia
  • A careful assessment of a patient’s social situation should be undertaken to help guide the disposition of the new onset symptomatic severe hyperglycemic patient. This assessment should include a careful evaluation of the social history, and account for risks of hypoglycemia, or HHS.


Quick Reference Guide to Diabetes Management from Diabetes Canada

Healthcare provider tools from Diabetes Canada


  1. Clerkship directors in emergency medicine. Hyperglycemia. Kenny Banh. November, 2019. Retrieved from:


  1. Initial management of blood glucose in adults with type 2 diabetes mellitus. Wexler, D; Nathan, D; Mulder, J. UpToDate. Topic updated August 7th, 2020. Retrieved from:


  1. Gosmanov AR, Gosmanova EO, Kitabchi AE. Hyperglycemic crises: diabetic ketoacidosis (DKA), and hyperglycemic hyperosmolar state (HHS). InEndotext [Internet] 2018 May 17. MDText. com, Inc.


  1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes care. 2009 Jul 1;32(7):1335-43.


  1. Weir GC, Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes. 2004 Dec 1;53(suppl 3):S16-21.


  1. Management of Hyperglycemic Crises in Patients With Diabetes. Abbas E. Kitabchi, Guillermo E. Umpierrez, Mary Beth Murphy, Eugene J. Barrett, Robert A. Kreisberg, John. Malone, Barry M. Wall. Diabetes Care Jan 2001, 24 (1) 131-153;


  1. Goguen, Jeannette, and Jeremy Gilbert. “Hyperglycemic emergencies in adults.”Canadian journal of diabetes42 (2018): S109-S114.


  1. EMOttawa. No thanks, I’m sweet enough: Nono-emergent hyperglycemia in the E. Rajiv Thavanathan, Seotember 27th, 2018. Retrieved from:


  1. Lipsombe L, Booth G, Butalia S, Dasgupta K, et al.Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults. Can J Diabetes 2018;42(Suppl 1):S88-S103.


  1. Sherifali D, Berard LD, Gucciardi E, MacDonald B, MacNeill G. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Self-management education and support. Canadian journal of diabetes. 2018 Apr 1;42:S36-41.


  1. Worswick J, Wayne SC, Bennett R, Fiander M, Mayhew A, Weir MC, Sullivan KJ, Grimshaw JM. Improving quality of care for persons with diabetes: an overview of systematic reviews-what does the evidence tell us?. Systematic reviews. 2013 Dec 1;2(1):26.


  1. Munoz, C., Villanueva, G., Fogg, L., Johnson, T., Hannold, K., Agruss, J., & Baldwin, D. (2011). Impact of a subcutaneous insulin protocol in the emergency department: Rush Emergency Department Hyperglycemia Intervention (REDHI).The Journal of Emergency Medicine,40(5), 493–8.


  1. Driver, B. E., Olives, T. D., Bischof, J. E., Salmen, M. R., & Miner, J. R. (2016). Discharge Glucose Is Not Associated With Short-Term Adverse Outcomes in Emergency Department Patients With Moderate to Severe??Hyperglycemia.Annals of Emergency Medicine,68(6), 697–705.e3.


  1. Yan, J. W., Gushulak, K. M., Columbus, M. P., van Aarsen, K., Hamelin, A. L., Wells, G. A., & Stiell, I. G. (2017). Risk factors for recurrent emergency department visits for hyperglycemia in patients with diabetes mellitus.International Journal of Emergency Medicine,10(1), 23.
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