Hyperglycemia


Article Author:
MIchelle Mouri


Article Editor:
Madhu Badireddy


Editors In Chief:
Silvio de Melo Jr.
Vittorio Giuliano
Truptesh Kothari


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
8/1/2019 1:13:14 PM

Introduction

The term "hyperglycemia" derived from the Greek hyper (high) + glykys (sweet/sugar) + haima (blood). Hyperglycemia is blood glucose greater than 125 mg/dL while fasting and greater than 180 mg/dL 2 hours postprandial. A patient has impaired glucose tolerance, or pre-diabetes, with a fasting plasma glucose of 100 mg/dL to 125 mg/dL. A patient is termed diabetic with a fasting blood glucose of greater than 125 mg/dL. [1][2]

When hyperglycemia is left untreated, it can lead to many serious limb and life-threatening complications that include damage to the eye, kidneys, nerves, heart, and the peripheral vascular system. Thus, it is vital to refer patients to the different specialists to obtain a baseline screening exam early on.

Etiology

Factors contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization, and increased glucose production. Glucose homeostasis is a balance between hepatic glucose production and peripheral glucose uptake and utilization. Insulin is the most important regulator of glucose homeostasis. [3][4]

Secondary cause of hyperglycemia include the following:

  • Destruction of the pancreas from chronic pancreatitis, hemochromatosis, pancreatic cancer, and cystic fibrosis.
  • Endocrine disorders that cause peripheral insulin resistance like Cushing syndrome, acromegaly, and pheochromocytoma.
  • Use of medications like glucocorticoids, phenytoin, and estrogens.
  • Gestational diabetes is known to occur in 4% of all pregnancies and is primarily due to the decreased insulin sensitivity.
  • Total parental nutrition and dextrose infusion.
  • Reactive, postoperatively or critically ill patients.

Major risk factors for hyperglycemia:

  • Weight more than 120% of the desired body weight.
  • Family history of type 2 diabetes.
  • Native Americans, Hispanics, Asian Americans, Pacific Islanders, or African Americans.
  • Presence of hyperlipidemia or hypertension.
  • History of gestational diabetes.[5]
  • Presence of polycystic ovarian syndrome.

Epidemiology

The incidence of hyperglycemia has increased dramatically over the last two decades due to increased obesity, decreased activity level, and an aging population. The prevalence is equal between men and women.  The countries with the greatest number of diabetics included China, India, United States, Brazil, and Russia. Hyperglycemia is more prominent in low to medium income households.

The latest data released by the Centers for Disease Control and Prevention indicate that there are nearly 30.5 million Americans with diabetes and nearly 84 million Americans with prediabetes. These numbers are set to increase significantly over the next decade.[6][7]

Pathophysiology

Hyperglycemia in a patient with type 1 diabetes is a result of genetic, environmental, and immunologic factors. These lead to the destruction of pancreatic beta cells and insulin deficiency. In a patient with type 2 diabetes, insulin resistance and abnormal insulin secretion lead to hyperglycemia.

According to recent studies, metabolic disturbances like type 2 diabetes mellitus increases the risk of cognitive decline and Alzheimer's dimentia. Alzheimer's dementia is also a risk factor for diabetes type 2. Recent studies have indicated these diseases are connected both at clinical and molecular levels. Like peripheral insulin resistance leading to type 2 diabetes, brain insulin resistance is linked to neuronal dysfunction and cognitive impairment in Alzheimer's dementia.[8]

History and Physical

The early symptoms of hyperglycemia include polyuria, polydipsia, and weight loss. As the patient's blood glucose increases, neurologic symptoms can develop. The patient may experience lethargy, focal neurologic deficits, or altered mental status. The patient can progress to a comatose state. 

Patients with diabetic ketoacidosis may present with nausea, vomiting and abdominal pain. They also may have a fruity odor and deep respirations, reflecting the compensatory hyperventilation.

Physical examination can reveal signs of hypovolemia like hypotension, tachycardia and dry mucus membranes. 

Evaluation

When evaluating a patient for hyperglycemia, the focus should be on the patient's cardiorespiratory status, mental status, and volume status. A bedside serum glucose can be obtained quickly. Testing includes serum electrolytes with the calculation of the anion gap, BUN and creatinine, and complete blood count. Urinalysis by dipstick assesses for glucose and ketones in the urine. Arterial blood gas or venous blood gas may be necessary if serum bicarbonate is substantially reduced.[9]

Blood Glucose Determination

To determine if the patient has developed type 2 diabetes the patient needs to have the following outcomes on these tests:

  • A fasting plasma glucose level of 126 mg/dL or higher.

  • A 2-hour plasma glucose level of 200 mg/dL or higher during a 75-g oral glucose tolerance test (OGTT).

  • A random plasma glucose of 200 mg/dL or higher in the presence of symptoms of hyperglycemia.

  • A hemoglobin A1c level of 6.5% or higher.

Treatment / Management

The treatment goals of hyperglycemia involve eliminating the symptoms related to hyperglycemia and reducing the long-term complications. Glycemic control in patients with type 1 diabetes is achieved by variable insulin regimen along with proper nutrition. Patients with type 2 diabetes are managed with diet and lifestyle changes as well as medications. Type 2 diabetes also may be managed on oral glucose-lowering agents. Patients with hyperglycemia need to be screened for complications including retinopathy, nephropathy, and cardiovascular disease. 

Goals of Treatment

Treatment goals are to reduce the the following complications associated with hyperglycemia:

  • Kidney and eye disease by regulation of blood pressure and lowering hyperglycemia.
  • Ischemic heart disease, stroke and peripheral vascular disease by control of hypertension, hyperlipidemia, and cessation of smoking.
  • Reduce risk of metabolic syndrome and stroke by control of body weight and control of hyperglycemia.

Patients who have hyperglycemia and are confirmed to have type 2 diabetes need to be referred to an endocrinologist. Unless there is a contraindication, the drug of first choice to lower hyperglycemia is metformin. In addition, some patients may require insulin therapy in combination with other agents.

Prevention of complications

To prevent complications of hyperglycemia, the following preventive approaches are recommended:

  • Refer to an ophthalmologist for yearly eye exams.
  • Monitor A1c levels every 3-6 months.
  • Check urinary albumin levels every 12 months.
  • Examine the feet at each clinic visit.
  • Maintain the Blood pressure to less than 130/80 mmHg.
  • Initiate statin therapy if patient has hyperlipidemia.

Some patients are prone to greater glycemic variability of their blood sugars within a day and also variability for the same time on different days, there by causing frequent episodes of hypoglycemia and hyperglycemia. These patients needs close monitoring by an endocrinologist with a treatment plan intended to reduce both the risks or at least maintain one risk while reducing the other.

Differential Diagnosis

Differential diagnosis of hyperglycemia include

1. Diabetes mellitus type 1 and 2.

2. Stress induced hyperglycemia.

3. Medications induced like steroids.

4. Other endocrinological conditions like acromegaly and cushing's disease.

5. Iatrogenic (IV fluids with dextrose and tube feeds).

Prognosis

The prognosis of individuals with hyperglycemia depends on how well the levels of blood glucose are controlled. Chronic hyperglycemia can cause severe life- and limb-threatening complications. Changes in lifestyle, regular physical exercise, and changes in diet are the keys to a better prognosis. Individuals who maintain euglycemia have a markedly better prognosis and an improved quality of life compared to individuals who remain hyperglycemic. Once the complications of hyperglycemia have developed, they are basically irreversible. Countless studies have shown that untreated hyperglycemia shortens lifespan and worsens the quality of life. Thus, aggressive lowering of hyperglycemia must be initiated, and patients must be closely followed. Studies suggest that one should try to achieve an A1C level of less than 7%. However, controlling blood sugars too tightly can result in hypoglycemia which is not well tolerated by elderly individuals who already may have a pre-existing cardiovascular disease.[10]

Complications

Complications of untreated or uncontrolled hyperglycemia over prolonged period of time include

1. Microvascular complications

  • Retinopathy
  • Nephropathy
  • Neuropathy

2. Macrovascular complications

  • Coronary artery disease
  • Cerebrovascular disease
  • Peripheral vascular disease

Postoperative and Rehabilitation Care

Hyperglycemia is common postoperatively. High blood sugars postoperatively is associated with higher perioperative complications so the target blood sugars should be kept around 140-180 mg/dL. Multiple teams take care of postoperative patients during their hospital stay, there by needing multidisciplinary team to create and follow protocols to treat hyperglycemia and decrease perioperative complications. [11]          

Consultations

Hyperglycemia can be managed by internists but if remains uncontrolled then consultation with a endocrinology is needed. 

Patients with diabetes are more prone to depression than those without diabetes. This is more so in newly diagnosed diabetics and young patients due to significsnt lifestyle changes that are needed. [12]

Deterrence and Patient Education

Patients diagnosed with diabetes needs comprehensive care by his treatment team in the first few months of diagnosis as management can be overwhelming and time consuming. Patients and family needs to be educated about testing blood sugar, taking medications especially insulin, going to their medical appointments, and lifestyle modifications which include diet and excercise. Patient needs to be given information for diabetes classes. 

Pearls and Other Issues

Patients with severe hyperglycemia should be assessed for clinical stability including mentation and hydration. Diabetic ketoacidosis and hyperglycemic hyperosmolar state are acute, severe disorders related to hyperglycemia. 

Patients confirmed with type 2 diabetes are faced with a life-long challenge to maintain euglycemia. This is not an easy undertaking and is also prohibitively expensive. Patients must be educated that making changes in their lifestyle can markedly improve their prognosis.

Enhancing Healthcare Team Outcomes

Diabetes management is very complex and time consuming. A very good team work is essential otherwise patient can be overwhelemed, leading to non-compliance with treatment which would further lead to irreversible complications. Patient and his family needs to work closely with his primay care physician, endocrinologist, dietician, and diabetic educator. Home health nursing services for disease management in the first few weeks might help. [13]


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Hyperglycemia - Questions

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Which is least likely to occur during the administration of total parenteral nutrition (TPN)?



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What does a random blood glucose of 200 mg/dl indicate?



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Which of the following causes polyuria?



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A 17-year-old male presents to the emergency department with altered mental status. He is protecting his airway however he has increased shallow respirations. He has no reported past medical history. His vitals are stable. What is the next step in the evaluation of this patient?



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A 35-year-old woman with a history of hypertension and obesity underwent hysterectomy for abnormal bleeding caused by uterine fibroids. Postoperatively her blood sugars were elevated, and the medical team was consulted for further management. On examination, vitals were stable, BMI of 38, her labs within normal limits except for hemoglobin of 11.0 g/dL and blood sugar of 180 mg/dL. Her hemoglobin A1c was 5.8%. She is currently eating and drinking well and not on any tube feeds or intravenous fluids. The patient denies a history of diabetes mellitus. Her blood sugars were closely monitored, and she was given insulin per sliding scale. Her blood sugars improved and were within normal limits at discharge. What is the most likely cause of her hyperglycemia?



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A 65-year old male with a known history of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease (COPD) presented with shortness of breath, productive cough with green phlegm, and wheezing for one week. He was admitted with a COPD exacerbation. His laboratory data on admission were within normal limits except for leukocytosis of 15,000/microL. Chest x-ray was negative for pneumonia. The patient was treated with scheduled and as needed ipratropium bromide/albuterol, IV methylprednisone (60 mg IV every 8 hrs), supplemental oxygen, and IV levofloxacin. He slowly but progressively improved, but his blood sugars were uncontrolled and were persistently above 200 mg/dL. The patient denies a history of diabetes mellitus, and his hemoglobin A1c was 5.5%. What is the most likely cause of his hyperglycemia?



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Hyperglycemia - References

References

Bashir M,Naem E,Taha F,Konje JC,Abou-Samra AB, Outcomes of type 1 diabetes mellitus in pregnancy; effect of excessive gestational weight gain and hyperglycaemia on fetal growth. Diabetes & metabolic syndrome. 2019 Jan - Feb     [PubMed]
Duggan EW,Carlson K,Umpierrez GE, Perioperative Hyperglycemia Management: An Update. Anesthesiology. 2017 Mar     [PubMed]
Yayan EH,Zengin M,Erden Karabulut Y,Akıncı A, The relationship between the quality of life and depression levels of young people with type I diabetes. Perspectives in psychiatric care. 2019 Jan 7     [PubMed]
Villegas-Valverde CC,Kokuina E,Breff-Fonseca MC, Strengthening National Health Priorities for Diabetes Prevention and Management. MEDICC review. 2018 Oct;     [PubMed]
Hammer M,Storey S,Hershey DS,Brady VJ,Davis E,Mandolfo N,Bryant AL,Olausson J, Hyperglycemia and Cancer: A State-of-the-Science Review. Oncology nursing forum. 2019 Jul 1;     [PubMed]
Yari Z,Behrouz V,Zand H,Pourvali K, New Insight into Diabetes Management: from Glycemic Index to Dietary Insulin Index. Current diabetes reviews. 2019 Jun 14;     [PubMed]
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Jacobsen JJ,Black MH,Li BH,Reynolds K,Lawrence JM, Race/ethnicity and measures of glycaemia in the year after diagnosis among youth with type 1 and type 2 diabetes mellitus. Journal of diabetes and its complications. 2014 May-Jun;     [PubMed]
Rawlings AM,Sharrett AR,Albert MS,Coresh J,Windham BG,Power MC,Knopman DS,Walker K,Burgard S,Mosley TH,Gottesman RF,Selvin E, The Association of Late-Life Diabetes Status and Hyperglycemia With Incident Mild Cognitive Impairment and Dementia: The ARIC Study. Diabetes care. 2019 Jul;     [PubMed]
Kubis-Kubiak AM,Rorbach-Dolata A,Piwowar A, Crucial players in Alzheimer's disease and diabetes mellitus: Friends or foes? Mechanisms of ageing and development. 2019 May 11;     [PubMed]
Shakya A,Chaudary SK,Garabadu D,Bhat HR,Kakoti BB,Ghosh SK, A Comprehensive Review on Preclinical Diabetic Models. Current diabetes reviews. 2019 May 10;     [PubMed]
Elgebaly MM,Arreguin J,Storke N, Targets, Treatments, and Outcomes Updates in Diabetic Stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2019 Jun;     [PubMed]
Goswami G,Scheinberg N,Schechter CB,Ruocco V,Davis NJ, IMPACT OF MULTIDISCIPLINARY PROCESS IMPROVEMENT INTERVENTIONS ON GLUCOMETRICS IN A NON-CRITICALLY ILL SETTING. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2019 Mar 13;     [PubMed]

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