Hypoglycemia In Diabetes Pathophysiology Prevalence And Prevention Pdf

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Hypoglycemia in Type 2 Diabetes—Consequences and Risk Assessment

Hypoglycemia in individuals with diabetes can increase the risk of morbidity and all-cause mortality in this patient group, particularly in the context of cardiovascular impairment, and can significantly decrease the quality of life. Hypoglycemia can present one of the most difficult aspects of diabetes management from both a patient and healthcare provider perspective. Strategies used to reduce the risk of hypoglycemia include individualizing glucose targets, selecting the appropriate medication, modifying diet and lifestyle and applying diabetes technology.

Using a patient-centered care approach, the provider should work in partnership with the patient and family to prevent hypoglycemia through evidence-based management of the disease and appropriate education. Hypoglycemia is both a clinical and physiologic condition that is associated with increased morbidity and all-cause mortality in individuals with both type 1 T1DM and type 2 diabetes T2DM [ 1 ].

An increasing body of evidence suggests that hypoglycemia is harmful to patients with diabetes both immediately and over time, particularly in terms of cardiovascular health [ 2 , 3 ]. While hyperglycemia can cause long-term complications, hypoglycemia can be imminently life threatening and significantly decrease the quality of life. Additionally, it is often difficult for patients to achieve the recommended glucose targets due to the fear of hypoglycemia or actual hypoglycemia.

However, using a patient-centered care approach and evidence-based practice, the provider can work in partnership with the patient to reduce the risk of hypoglycemia. This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.

Several large-scale clinical trials have demonstrated the incidence and prevalence of hypoglycemia in patients with both T1DM and T2DM. The prevalence of hypoglycemia in patients with T1DM has been reported to range from 62 [ 4 ] to [ 5 ] episodes per patient-years. Individuals with T1DM may experience an average of two symptomatic hypoglycemia episodes per week and one to three disabling, potentially life-threatening episodes per year [ 1 , 6 ].

The risk of hypoglycemia in individuals with T2DM is much lower and is often associated with advanced diabetes with endogenous insulin deficiency. The prevalence of hypoglycemia in T2DM ranges from 0 [ 7 ] to 73 [ 5 ] episodes per patient-years. Rates of severe hypoglycemia are more common among older adults and those with chronic conditions, such as chronic kidney disease, cardiovascular disease CVD , congestive heart failure, depression and higher glycated hemoglobin HbA1c levels, as well as among those who are on insulin or take secretagogues [ 6 ].

Hypoglycemia poses an economic burden to healthcare resources. Published data also suggest that hypoglycemia directly impairs health-related quality of life in patients with T2DM and that this impairment becomes increasingly pronounced with increasing severity and frequency of the hypoglycemic episodes [ 10 , 11 ].

This relationship has not been consistently shown in adult patients with T1DM [ 11 ], but it has been more clearly documented in pediatric and adolescent patients [ 12 ]. Hypoglycemia is known to contribute to morbidity and mortality in the clinical setting of diabetes [ 2 ]. This risk is primarily cardiovascular related and is seen most often in patients with diabetes who are treated with insulin [ 13 ]. Hypoglycemia causes increases in blood pressure, stroke volume, cardiac output and myocardial contractility, all of which may cause reduced cardiovascular functioning over time [ 14 ].

The results of a study of patients suggested that the crude incidence rates of CVD and death were higher in persons with hypoglycemia than in those without, even after adjusting for potential confounding variables [CVD: In individuals with diabetes, hypoglycemia often results from excess insulin or the inability to raise the blood glucose BG level through endogenous or exogenous methods [ 17 ].

In order to understand the pathophysiology of hypoglycemia, it is imperative to understand normal glucose homeostasis.

The regulation of glucose is dependent on multiple systems, including the renal, hepatic, pancreatic and neuroendocrine systems. Any deficiencies within these systems for example end-stage renal disease or liver failure can affect the physiologic response to hypoglycemia. The first counter-regulatory measure is the halting of insulin production. At this glucose level, the body also begins to release endogenous hormones, such as epinephrine, cortisol and growth hormone, in an attempt increase BG.

This chain of events is dependent on the proper functioning of the pancreatic alpha cells, liver and kidneys. Recurrent and frequent hypoglycemia over time can lead to hypoglycemic-associated autonomic failure HAAF , a pathophysiologic process in which sympathoadrenal processes no longer trigger symptoms of hypoglycemia, causing potentially dangerous asymptomatic hypoglycemia [ 17 ].

In , The American Diabetes Association ADA and the Endocrine Society assembled a workgroup to address the knowledge gaps related to the definition, implications and understanding of hypoglycemia [ 19 ]. Patients with hypoglycemia unawareness may experience non-specific symptoms, such as waking up in the morning with a headache, a high blood glucose level in the morning Somogyi effect or nighttime sweating. HAAF is a serious condition in which repeated hypoglycemic episodes fail to trigger the protective autonomic system response, leading to asymptomatic hypoglycemia.

The HAAF phenomenon includes the failure of insulin levels to decrease in the presence of hypoglycemia, failure of glucagon secretion, and lack of epinephrine secretion [ 22 ]. HAAF is exacerbated by frequent or recent hypoglycemia as well as sleep or exercise [ 22 ].

When the regulatory system is working correctly, these systems ensure an adequate glucose supply to the brain in times of hypoglycemia. When HAAF is present, severe hypoglycemia may occur. Important factors to consider in prevention include patient awareness of hypoglycemia, individualized glucose targets, self-monitoring of blood glucose SMBG , diet, exercise and medication regimen. Many patients need reassurance for this type of approach, as some patients are fearful of high glucose levels, even over the short term, and associated diabetes complications.

In the patient-centered approach to glycemic control, the ADA recommends less strict glycemic goals when the benefits of tight glycemic control outweigh the risks for hypoglycemia. A higher HbA1c goal is reasonable for those with hypoglycemic unawareness and chronic kidney disease, the elderly and those with CVD. Renal function should be monitored, as worsening renal function is associated with a decline in insulin requirements.

For patients at high risk of hypoglycemia, it may be prudent to change anti-hypertensive agents. A visit to a certified diabetes educator to review glucose logs along with diet and activity logs can help discern important glucose trends and hypoglycemia triggers.

For those patients who are working on losing weight, a h diet recall should be included to assess whether insulin mealtime doses should be altered. Weight loss improves insulin sensitivity and may lead to a necessary reduction in insulin doses.

Lowering the insulin dose or increasing food intake for the meal before the planned exercise are strategies to prevent hypoglycemia, and both interventions may be necessary [ 28 ]. Many of the new agents to treat diabetes are less likely to cause hypoglycemia than the older classes of medications.

In addition to metformin, glucagon-like peptide-1 GLP-1 agonists, dipeptidyl peptidase-4 DPP-IV inhibitors and sodium—glucose cotransporter 2 SGLT-2 inhibitors are all excellent choices for people who are at risk of hypoglycemia. Older medication classes, such as sulfonylureas and meglitinides, should generally be avoided by patients who are at high risk for hypoglycemia.

An understanding of the pharmacokinetic profiles of the various insulin preparations is important when the aim is to modify insulin dosing to prevent hypoglycemia.

In addition, there are insulins that are associated with less frequent hypoglycemia, and thus a change in insulin preparation may help reduce the frequency of low glucose readings.

Most notably, the intermediate-action insulin isophane, also known as NPH, and regular insulin are associated with more frequent hypoglycemic episodes than the long-acting glargine, detemir and degludec insulins, particularly at night. Continuous glucose monitors CGMs have revolutionized the treatment and prevention of hypoglycemia.

CGMs also identify important glucose trends, such impending hypoglycemia, that allow for early treatment and prevention of hypoglycemia. CGM data can be downloaded and reviewed online or in a clinic setting to help providers identify trends to allow for more accurate medication modification.

The CGMs also alarm at night, alerting patients and families to hypoglycemia. There is a strong body of evidence noting that the use of CGM results in less frequent hypoglycemic episodes when compared to conventional SMBG, while improving and stabilizing overall glycemic control [ 30 ]. Patients find that CGM can help improve their quality of life and self-efficacy in managing hypoglycemia. However, CGMs are less accurate during times of rapid glucose excursions such as right after a meal [ 30 ].

Patients may find the false alarms and need for calibration to be annoying alarm fatigue , and the cost of a CGM may be prohibitive for some patients [ 31 ]. Patients likely to benefit from CGMs include individuals with required manual dexterity to insert and operate the sensor system and individuals with multiple risk factors for hypoglycemia older age, chronic kidney disease, autonomic neuropathy, CVD.

Insulin pumps continuous subcutaneous insulin infusion have long been recognized as a tool that can decrease hypoglycemia while improving glycemic control. CGMs are also integrated into insulin pump technology and include an alarm and automatic 2-h suspension of the insulin infusion for hypoglycemia, which is particularly helpful at night. The sensor-augmented pumps can reduce the frequency of hypoglycemic episodes while maintaining good glucose control [ 33 ].

Other strategies for preventing hypoglycemia include a CGM-augmented pump that infuses both insulin and glucagon [ 35 ]. Hypoglycemia causes harm to people with diabetes, creating cardiovascular impairment and an increased risk of cardiovascular morbidity and all-cause mortality [ 19 ].

Further, hypoglycemia significantly impacts the quality of life of patients with diabetes and can limit optimal glucose control.

A patient-centered approach is imperative to achieve optimal glucose control while avoiding hypoglycemia and its harmful effects. A patient-centered approach is one that is based on shared medical decision-making among the patient, family and healthcare provider and uses individualized approaches to problem solving and diabetes management planning.

Education aimed at recognizing the signs and symptoms of hypoglycemia is imperative for both patients and families. Appropriate teaching includes individual risk factors, prevention, and treatment of hypoglycemia. In addition, healthcare providers must work diligently with patients and families to identify and eradicate hypoglycemia by using appropriate glucose targets and medications and modifying lifestyle.

Cryer P. Hypoglycemia in diabetes: pathophysiology, prevalence, and prevention. International Hypoglycaemia Study Group. Minimizing hypoglycemia in diabetes. Diabetes Care. Association of severe hypoglycemia with cardiovascular disease and all-cause mortality in older adults with diabetes: the atherosclerosis risk in communities ARIC study.

Google Scholar. Epidemiology of severe hypoglycemia in the diabetes control and complications trial. Am J Med. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Severe hypoglycemia requiring medical intervention in a large cohort of adults with diabetes receiving care in US integrated health care delivery systems: — P cost of hypoglycemia associated with diabetes mellitus: a systematic review of the literature.

Economic impact of severe and non-severe hypoglycemia in patients with type 1 and type 2 diabetes in the United States.

J Med Econ. Assessment of severity and frequency of self-reported hypoglycemia on quality of life in patients with type 2 diabetes treated with oral antihyperglycemic agents: a survey study. BMC Res Notes. Self-report of hypoglycemia and health-related quality of life in patients with type 1 and type 2 diabetes.

Endocr Pract. Management of hypoglycemia in children and adolescents with type 1 diabetes mellitus. Curr Diabetes Rep. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study.

Hypoglycemia and cardiovascular risks. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. Longterm mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway.

Practical Approaches to Diagnosing, Treating and Preventing Hypoglycemia in Diabetes

Jay H. In November , the Centers for Disease Control and Prevention presented data on emergency hospitalizations because of adverse drug reactions. A total of 24, hospitalizations resulted from these medications. Hypoglycemia is common in diabetes. It can result from insulin treatment but also can occur in those taking oral medications. Although intensive glucose control has been shown to prevent microvascular complications and potentially decrease macrovascular complications in some populations, this benefit must be balanced with the detrimental effects of hypoglycemia. In fact, hypoglycemia may be the largest barrier to normalization of glucose control in diabetes.

NCBI Bookshelf. Endotext [Internet]. Hypoglycemia, caused by treatment with a sulfonylurea, a glinide, or insulin coupled with compromised defenses against the resulting falling plasma glucose concentrations, is the limiting factor in the glycemic management of diabetes. It causes recurrent morbidity in most people with type 1 diabetes mellitus T1DM and many with advanced type 2 diabetes mellitus T2DM and is sometimes fatal; it limits maintenance of euglycemia over a lifetime of diabetes; and it impairs physiological and behavioral defenses against subsequent hypoglycemia. In addition to drug selection and application of diabetes treatment technologies, minimizing hypoglycemia in diabetes includes acknowledging the problem, considering each of the risk factors and applying the principles of intensive glycemic therapy.

Hypoglycemia is uncommon in the general, nondiabetic population but occurs frequently in persons with diabetes treated with insulin or insulin secretagogues. Thus, iatrogenic hypoglycemia explains the majority of cases among persons with type 1 diabetes T1DM. Since T1DM is characterized by absolute insulin dependence, the current imperfections in insulin replacement therapies often lead to a mismatch between caloric supply and circulating insulin levels, thus increasing the risk for glycemic fluctuations. Hypoglycemia is the limiting factor to excellent glycemic control in insulin-treated subjects. Recent measurements using continuous glucose monitoring reveal an alarming rate of daytime and nocturnal episodes of hypoglycemia in patients with T1DM.

PDF | The importance of strict glycemic control to limit the risk of type 2 diabetes, the actual prevalence of hypoglycemia is likely to escalate.

Pdf Hypoglycemia In Diabetes Pathophysiology Prevalence And Prevention 2012

Focuses on the prevention and treatment of hypoglycemia with careful attention to glycemic management. Intended for diabetes researchers and medical professionals who work closely with patients with diabetes, this newly updated and expanded edition provides new perspectives and direct insight into the causes and consequences of this serious medical condition from one of the foremost experts in the field. Using the latest scientific and medical developments and trends, readers will learn how to identify, prevent, and treat this challenging phenomenon within the parameters of the diabetes care regimen.

Hypoglycemia is the acute complication of diabetes mellitus and the commonest diabetic emergency and is associated with considerable morbidity and mortality. It can be caused by too much insulin intake or oral hypoglycemic agents, too little food, or excessive physical activity. The level of glucose that produces symptoms of hypoglycemia varies from person to person and varies for the same person under different circumstances. It characterized by sweating, tremor, tachycardia, palpitation, nervousness, hunger, confusion, slurred speech, emotional changes, double vision, drowsiness, sleeplessness, and often self-diagnosed which may leads to serious symptoms of seizure, cognitive impairment, coma and death. The immediate treatment of hypoglycemia should be known by all the diabetic patients, so that need for hospitalization could be avoided.

Pdf Hypoglycemia In Diabetes Pathophysiology Prevalence And Prevention 2012