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Sunday, January 21, 2018

Hypoglycemia, as a Clinical Event in Diabetic Patients.

Due to the effectiveness of the normal defenses against falling plasma glucose concentrations, hypoglycemia is an uncommon clinical event.

However, Hypoglycemia is a fact of life for most persons with type 1 diabetes and many with type 2

Although persons with diabetes are not spared the risk for the same hypoglycemic disorders as those without diabetes, the vast majority of their hypoglycemic episodes are the result of treatment of their diabetes.

Iatrogenic hypoglycemia associated with diabetes medications are among the most common causes of hypoglycemia in patients with diabetes.

Furthermore, the pathophysiology of hypoglycemia in diabetes is distinct, and the diagnostic and management approaches are different from those in individuals without diabetes.

Hypoglycemia may also result from certain seldom causes such as pancreatic or non-islet cell tumors, autoimmune conditions, organ failure, endocrine disease, inborn errors of metabolism, dietary toxins, alcohol consumption, stress, infections and miscellaneous conditions (such as sepsis, starvation, severe excessive exercise)

What then is hypoglycemia?

Both the American Diabetes Association (ADA) and the European Medicines Agency have defined hypoglycemia as
“any abnormally low plasma glucose concentration that exposes the subject to potential harm” with a proposed threshold plasma glucose value <3.9 mmol/L (<70 mg/dL).
The operational threshold for hypoglycemia is defined as “that concentration of plasma or whole blood glucose at which clinicians should consider intervention, based on the evidence currently available in literature”. 

This threshold is currently believed to be a blood glucose value of <2.2mmol/L(40 mg/dL),  (plasma glucose <2.5mmol/L ( 45 mg/dL).

An Endocrine Society Clinical Practice Guideline recommend evaluation and management of hypoglycemia only in patients in whom Whipple’s triad—symptoms, signs, or both consistent with hypoglycemia, a low plasma glucose concentration, and resolution of those symptoms or signs after the plasma glucose concentration is raised—is documented. 

Physiology and pathophysiology

Glucose is an obligate metabolic fuel for the brain under physiological conditions. Because the brain cannot synthesize glucose, use physiological circulating concentrations of alternative fuels effectively, or store more than a few minutes’ supply as glycogen, maintenance of brain function, and ultimately survival, requires a virtually continuous supply of glucose from the circulation.

That, in turn, requires maintenance of the plasma glucose level within the physiological range.
This is effectively maintain by counter-regulatory mechanisms which rapidly prevent or correct hypoglycemia

Because external losses are normally negligible, hypoglycemia develops when the sum of glucose utilization from the circulation exceeds the sum of glucose delivery into the circulation (from ingested carbohydrates and hepatic and renal glucose production(gluconeogenesis).

Because of the capacity to increase endogenous glucose production substantially, hypoglycemia is typically the result of absolutely low rates of glucose production or rates of glucose production that are low relative to high rates of glucose utilization.

General differential diagnosis

Causes of hypoglycemia in patient without DM:
Drugs are the most common cause of hypoglycemia. 
Critical illnesses
Hormone deficiencies
Nonislet cell tumours
In the absence  of these, then consider:
Endogenous hyperinsulinism, in these measure:( Insulinoma, Nesidioblastosis)
Plasma glucose,
Circulating oral hypoglycaemic agents
Insulin Abs

Nevertheless, some hypoglycaemic episodes remain unexplained, and inborn errors of metabolism (IEM) should be considered, particularly in cases of multisystemic involvement. 
In children, IEM are considered a differential diagnosis in cases of hypoglycaemia. 
In adulthood, IEM-related hypoglycaemia can persist in a previously diagnosed childhood disease. 
Hypoglycaemia may sometimes be a presenting sign of the IEM.
 A) Short stature, 
b) hepatomegaly, 
c) hypogonadism, 
d) dysmorphia or 
e) muscular symptoms , are signs suggestive of IEM-related hypoglycaemia. 
They are usually classified into 3 main groups:
 1) intoxication diseases
2) diseases linked to energy deficiency
3) diseases due to degradation or synthesis defect of complex molecules
The clinical presentations of these disorders are very diverse and can encompass any symptoms at any age in any scenario with any mode of inheritance.

Hypoglycemia in diabetic patients.

Hypoglycemia is one of the most important complications of diabetes treatment. 
The risk of severe hypoglycemia is higher in elderly patients, those having comorbidities such as vascular disease, liver disease or renal failure, pregnant women and in children with type 1 diabetes. 

Moreover, in type 2 diabetes, progressive insulin deficiency, longer duration of diabetes, and tight glycemic control increase the risk of hypoglycemia as much as type 1 diabetes. 
Episodes hypoglycemia may lead to impairment of counter-regulatory system, with the potential of development of hypoglycemia unawareness. 

So, hypoglycemia may increase the vascular events even death in addition to other possible detrimental effects. 

Glycemic control should be individualized based on patient characteristics with some degree of safety. 
Recognition of hypoglycemia risk factors, blood glucose monitoring, selection of appropriate regimens and educational programs for healthcare professionals and patients with diabetes are the major issues to maintain good glycemic control, minimize the risk of hypoglycemia, and prevent long- term complications.

Epidemiology of hypoglycaemia in DM

For diabetic patients hypoglycemia is a fact of life. 
Approximately 90% of all patients who receive insulin have experienced hypoglycemic episodes. 
An estimated 2–4% of deaths of type 1 diabetes mellitus have been attributed to hypoglycemia. This is likely to be under-estimation
The frequency of hypoglycemia is lower in people with type 2 diabetes than Type 1.
In type 2 DM the risk of severe hypoglycemia is low in the first few years (7%) and that risk increases to 25% later in the course of diabetes. 
The incidence of hypoglycemia also could be affected by how tight glycemic control is performed. 
In a survey of diabetes patients (16-94 years of age) in Germany, UK and Spain showed that severe hypoglycemic events represent a substantial burden on national healthcare systems. 
Overall, insufficient food consumption was the most common cause identified for severe hypoglycemia (43% in T1DM and 47% in T2DM).
Physical exercise (24% and 23%),
Insulin dose miscalculation (24% and 16%), 
Stressful situations (12% and 17%), 
Oscillating blood glucose levels (9% and 8%) and 
Impaired hypoglycemia awareness (8% and 5%) in T1DM and T2DM, respectively.
Hypoglycaemia unawareness is defined as ‘the onset of neuroglycopenia before the appearance of autonomic warning symptoms’. 
Clinically, this manifests as the inability to perceive hypoglycaemia by symptoms.

Hypoglycemia in elderly

Hypoglycemia is a common problem in old people with diabetes. Aging modifies the cognitive, symptomatic, and counter-regulatory hormonal responses to hypoglycemia. The effect of aging on increased risk of unawareness or severe episodes of hypoglycemia has also been recognized. Although hypoglycemia in the elderly is the most common complication of tight glycemic control, multiple co-morbidities like chronic liver disease, renal impairment, chronic heart disease, malnutrition and polypharmacy may increase risk of this complication.

Hypoglycemia in children and adolescents

Hypoglycemia is one of the most common acute complications of insulin therapy in children and adolescents with diabetes. The incidence of hypoglycemia is reported to be between 3 and 27 episodes per 100 patient- year in children with type 1diabetes. The recurrent and severe episodes of hypoglycemia cause hypoglycemic fearfulness and emotional morbidity both for patients and their parents, which could act as a limiting factor in achievement of good glycemic control.

Prevention of hypoglycemia in diabetic subjects

While achieving and maintaining the optimal glycemic control is one of the principal aims of prevention and management of diabetes complications, hypoglycemia remains a major challenge. 
Obviously prevention of hypoglycemia is preferable to its treatment since as compared with a reactive approach, prevention is much more likely to avoid severe events and economic burden.
The prevention of hypoglycemia requires some principles consideration. These principles include:
 1) Education for both diabetic care personals and the patient
2) diabetes self management (supported by education and empowerment);
3) self- monitoring of blood glucose or continuous glucose sensing; 
4) flexible and appropriate insulin or other drug regimens; 
5) individualized glycemic goals; 
6) consideration of known risk factors of hypoglycemia; 
7) professional support and guidance.

1 comment:

  1. Diabetes,it's a group of metabolic diseases,where a person has high blood glucose levels.I'm facing this disease. I'm suffering with this disease from the year 2017.People who has diabetes,should avoid carbs food as well as need to take consultant for diabetes treatment


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