Hypoglycaemia in the Elderly Diabetics

INTRODUCTION

The elderly population is one of the most discussed global phenomena in the present-day. Countries with an increasing population like India have a large number of people aged 60 years or more. In the last five decades, the number of people over 60 years has tripled and in short duration. According to census 2011, older people constitute 8.14% of the total population. The projected population of those over 60 years in the next four censuses is 133.32 million (2021), 178.59 (2031), 236.01 million (2041) and 300.96 million (2051)¹ .

Diabetes is a critical health condition for the ageingpeople; at least 20% of patients over the age of 65 years have diabetes, and this number is expected togrowfurther in the coming times. Older individuals with diabetes have higher rates of premature death, functional disability, and coexisting illnesses, such as hypertension, coronary heart disease, and stroke than those without diabetes. Older adults with diabetes are also at a higherrisk than other older adults for several common geriatric syndromes, such as cognitive impairment, urinary incontinence, injurious falls, persistent body pain and are likely to be on polypharmacy. They are at a higher risk of hypoglycemia for many reasons, including insulin deficiency and progressive renal insufficiency. They tend to have higher rates of unidentified cognitive deficits, causing difficulty in complex self-care activities (e.g., glucose monitoring, and adjusting insulin doses). These deficits have been associated with increased risk of hypoglycemia and with severe hypoglycemia linked to increased dementia.

Hypoglycemic events monitored meticulously, and glycemic targets need to be adjusted to accommodate the changing requirements of the older adult^2,3. One needs to look at the individual to best balance risk versus benefit associated with the tight glycemic control. Benefits of intensive therapy to lower HbA1c must always weigh against the higher risk of disabling and unpredictable hypoglycemia, as the geriatric population is less likely to take advantage of reducing the risk of microvascular complications and more likely to suffer serious adverse effects from hypoglycemia⁴.

Definition

Hypoglycemia represents blood sugar decreases below normal levels. This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures or death. A feeling of hunger, sweating, shakiness and weakness may also be present. Symptoms typically come on quickly.

The glucose level that defines hypoglycaemia is variable; in people with diabetes, level below 3.9 mmol/L (70 mg/dL) is diagnostic. In adults, symptoms related to low blood sugar, low blood sugar at the time of symptoms and improvement when blood sugar restored to normal confirms the diagnosis. Otherwise, a level below 2.8 mmol/L (50 mg/dL) after not eating or the following exercise may be used. In new-borns, a level below 2.2 mmol/L (40 mg/dL), or less than 3.3 mmol/L (60 mg/dL) if symptoms are present, indicates hypoglycemia. Other tests that may be useful in determining the cause include insulin and C-peptide levels in the blood.

Aetiology

The most common cause of hypoglycaemia is medications used to treat diabetes mellitus such as insulin and sulfonylureas. The risk is higher in people with diabetes who have eaten less than usual, exercised more than usual or have consumed alcohol. Other causes of hypoglycaemia include kidney failure, certain tumours, such as insulinoma, liver disease, hypothyroidism, starvation, an inborn error of metabolism, severe infections, reactive hypoglycaemia and some drugs including alcohol. Low blood sugar may occur in otherwise healthy babies who have not eaten for a few hours. Hypoglycaemia may induce symptoms or signs such as altered mental status and sympathetic nervous system stimulation. This condition typically arises from abnormalities in the mechanisms involved in glucose homeostasis.

Manifestations

The glucose level at which an individual becomes symptomatic is highly variable (threshold generally at < 50 mg/dL). Carefully review the patient’s medication and drug history for potential causes of hypoglycaemia.

The patient’s medical and social history may reveal the following:

• Diabetes mellitus, renal insufficiency/failure, alcoholism, hepatic cirrhosis/failure, other endocrine diseases, or recent surgery

• Central nervous system: Headache, confusion, personality changes

• Ethanol intake and nutritional deficiency

• Weight reduction, nausea and vomiting

• Fatigue, somnolence

• Neurogenic or Neuroglycopenic symptoms of hypoglycaemia may be categorised as follows:

• Neurogenic (adrenergic) (sympathoadrenal activation) symptoms: Sweating, shakiness, tachycardia, anxiety, and a sensation of hunger

• Neuroglycopenic symptoms: Weakness, tiredness, or dizziness; inappropriate behaviour (sometimes mistaken for inebriation), difficulty with concentration; confusion; blurred vision; and, in extreme cases, coma and death

Reactive hypoglycemia includes the following features:

• More common in overweight and obese people who are insulin-resistant

• Maybe a frequent precursor to type 2 diabetes

• Possible higher risk in patients with a family history of type 2 diabetes or insulin-resistance syndrome

The actual loss of consciousness is highly suggestive of an aetiology other than reactive hypoglycaemia.

Gestational hypoglycaemia may have the following features⁵ :

• More frequent in women younger than 25 years

• More frequent in women with a pre-existing medical condition

• Less frequent in women whose pre-pregnancy body mass index ≥30 kg/m2

• Higher risk of preeclampsia/eclampsia in affected women

Symptoms

Neurogenic or neuroglycopenic symptoms: Earlier, symptoms of hypoglycaemia may be categorised as neurogenic (adrenergic) or neuroglycopenic. Sympatho-adrenal activation symptoms include sweating, shakiness, tachycardia, anxiety, and a sensation of hunger. Neuroglycopenic symptoms include weakness, tiredness, or dizziness; inappropriate behaviour (sometimes mistaken for inebriation), difficulty with concentration; confusion; blurred vision; and, in extreme cases, coma and death. The timing of onset of symptoms relative to the time of meal ingestion is crucial in the evaluation of a patient with hypoglycaemia.

Fasting hypoglycaemia typically occurs in the morning before eating or during the day, particularly in the afternoon if meals are missed or delayed. Postprandial hyperglycaemia typically occurs 2-4 hours after eating food, especially when meals contain high levels of simple carbohydrates.

Postprandial symptoms are typically due to reactive causes, but some patients with insulinoma also may present with postprandial symptoms. About 4-6 hours after food ingestion, plasma glucose concentrations are 80-90 mg/dL, and rates of glucose utilisation and production are approximately 2 mg/kg/min. Glucose production is primarily (70-80%) from hepatic glycogenolysis, with a lesser contribution (20- 25%) from hepatic gluconeogenesis. A study by Feil et al. found a high risk of hypoglycaemia among patients with dementia and cognitive impairment⁶ .

Reactive hypoglycaemic symptoms^6,7

Reactive hypoglycaemia seldom causes glucose levels to drop low enough to induce severe neuroglycopenic symptoms; therefore, a history of exact loss of consciousness is highly suggestive of an aetiology other than reactive hypoglycaemia. Reactive hypoglycaemia has been suggested to be more common in overweight and obese people who are insulin-resistant, and it may be a frequent precursor to type 2 diabetes. Therefore, patients who have a family history of type 2 diabetes or insulin-resistance syndrome (i.e., hypertension, hyperlipidaemia, obesity) may be at higher risk for developing hypoglycaemia.

Gestational hypoglycemia^6,7

In a study of maternal hypoglycaemia, Pugh et al found that hypoglycaemia occurred more frequently in women younger than 25 years and those who had a pre-existing medical condition7 . Hypoglycaemia was less frequent in women whose pre-pregnancy body mass index (BMI) was ≥ 30 kg/m2. The investigators also found that patients with hypoglycaemia were at higher risk of preeclampsia/eclampsia.

Physical Examination

Physical findings are nonspecific in hypoglycaemia and generally, are related to the central and autonomic nervous systems. Assess vital signs for hypothermia, tachypnoea, tachycardia, hypertension, and bradycardia (neonates).The head, eyes, ears, nose, and throat (HEENT) examination may indicate blurred vision, pupils normal to fixed and dilated, icterus (usually cholestatic due to hepatic disease), and parotid pain (due to endocrine causes).Cardiovascular disturbances may include tachycardia (bradycardia in neonates), hypertension or hypotension, and dysrhythmias. Neurologic conditions include coma, confusion, fatigue, loss of coordination, combative or agitated disposition, stroke syndrome, tremors, convulsions, and diplopia.

Respiratory disturbances may include dyspnoea, tachypnoea, and acute pulmonary oedema. Gastrointestinal disturbances may include nausea and vomiting, dyspepsia, and abdominal cramping. The patient’s skin may be diaphoretic and warm or show signs of dehydration with a decrease in turgor. Symptoms of hypoglycaemia are fewer in elderly persons, and they frequently appear at a lower threshold of plasma glucose than in younger persons.

Diagnostic considerations

Because the consequences of hypoglycaemia, the event can be devastating and an antidote is readily available, diagnosis and treatment must be rapid in any patient with suspected hypoglycaemia, regardless of the cause. Patients with no previous history of hypoglycaemia require a complete workup to find a potentially treatable disease. Careful consideration should be given to all diabetic patients presenting with hypoglycaemia. New medications, activity changes, and infection should be considered. Early in the course of non–insulin-dependent diabetes, patients may experience episodes of hypoglycaemia several hours after meals. The symptoms generally are brief and respond spontaneously. Conditions such as morning vomiting sickness, ingestion of ethanol-containing mouthwash or cologne (children), gastric surgery, potassium administration during periodic attacks of paralysis, excessive muscular activity, diarrhoea (childhood) can also cause hypoglycaemia.

The following should be considered when evaluating a patient with hypoglycemia⁶ :

• Hepatic disease: (e.g., hepatic failure, cirrhosis, galactose intolerance, fructose intolerance, glycogen storage diseases)

• Transient ischemic attacks

• Cardiac dysrhythmia

• Endocrine disorders (e.g., pheochromocytoma, Addison disease, glucagon deficiency, carcinomas, extrahepatic tumours)

• Substance abuse (e.g., cocaine, ethanol, salicylates, beta-blockers, pentamidine)

• Hypoglycaemic agents (e.g., insulin, oral hypoglycaemic agents)

• Nutritional disorders (e.g., prolonged starvation before anaesthesia, protein-calorie malnutrition, L-leucine-sensitive hypoglycaemic defect in children, low-calorie ketogenic diet, renal disease)

• Autoimmune disorders (e.g., Graves’ disease)

• Central nervous system (CNS) disorders

• Psychogenic

Differential Diagnosis

• Addison Disease

• Adrenal Crisis

• Alcoholism

• Anxiety Disorders

• Cardiogenic Shock

• Hypopituitarism (Panhypopituitarism)

• Insulinoma

• Pseudo hypoglycemia

Approach (investigations as necessary)^7,8:

Search for a source of infection. Studies should be considered to rule out the possibility of a concurrent occult infection contributing to the new hypoglycaemic episode (e.g., complete physical examination, chest radiography (particularly in diabetic patients presenting with hypoglycaemia), urinalysis, blood cultures). Check liver function tests, serum insulin levels, and cortisol and thyroid levels. Proinsulin represents less than 20% of total immunoreactive insulin typically; in patients with islet-cell tumours, proinsulin may contribute as much as 70% of insulin immunoreactivity.

Other causes of hypoglycaemia should be adequately investigated (see Differentials). For example, a morning cortisol level determination and adrenocorticotropic hormone (ACTH) stimulation testing should be performed if adrenal insufficiency is suspected.

Glucose and Insulin Levels: During hypoglycaemic episodes, patients should test their glucose at home to document hypoglycaemia that is occurring with the episodes. Take into consideration that meter readings may not be accurate enough to establish the diagnosis. Test glucose and insulin levels simultaneously to document low glucose levels occurring in conjunction with inappropriate insulin levels. Keep in mind that whole blood glucose values may be spuriously low in polycythaemia rubra-vera because of the unequal distribution of glucose between erythrocytes and plasma, excessive glycolysis by erythrocytes, or both. Low blood glucose values in leukaemia are due to excessive glycolysis by leukocytes and in haemolytic crisis from excessive glycolysis by nucleated erythrocytes.

Oral glucose tolerance test: Administer an oral glucose tolerance test if reactive hypoglycaemia is suspected. An oral glucose tolerance test provides little benefit for the evaluation of fasting hypoglycaemia. Perform the test for 5 hours while simultaneously testing glucose and insulin levels. To be meaningful, low blood sugar (< 50 mg/ dL [< 2.78 mmol/L]) during the test should be accompanied by typical symptoms. Response to a mixed meal may be more representative.

72-Hour fasting plasma glucose: A supervised fast is the most reliable diagnostic test for the evaluation of fasting hypoglycaemia. Continue the fast for as long as 72 hours or until symptoms develop in the presence of hypoglycaemia (blood sugar < 45 mg/dL (2.5 mmol/L) for women; < 55 mg/ dL (3.05 mmol/L) for men). Obtain simultaneous insulin levels every 6 hours, when glucose is low and when symptoms develop. Also, measure the beta-hydroxybutyrate serum level. Glucose and glucagon must be administered after blood sample withdrawal to abort hypoglycaemic symptoms. The diagnosis of insulinoma is likely if the patient, at the conclusion of the fast, has neuroglycopenic symptoms, a fall in plasma glucose to less than 45 mg/dL (< 2.5 mmol/L), inappropriately elevated beta-cell polypeptides (insulin, proinsulin, and C-peptide levels), and a beta-hydroxybutyrate level of less than 2.7 mmol/L.For overnight fasting plasma glucose levels, symptoms of hypoglycaemia may develop when the blood sugar is below 60 mg/dL (3.33 mmol/L).

C-Peptide Levels: Obtain C-peptide levels any time an elevated insulin level is obtained. Endogenous hyperinsulinemia from insulinoma is associated with elevated C-peptide concentrations with concurrent hypoglycaemia. Exogenous hyperinsulinemia from injected insulin results in low concentrations of C-peptide, both because of the effect of the associated hypoglycaemia and because of the direct suppressive effect of insulin on the pancreatic beta cell. C-peptide levels are elevated in insulinoma, average or low with exogenous insulin, and elevated with oral sulfonylureas.

Radiologic Studies: For the evaluation of insulinomas, computed tomography (CT) scanning and ultrasonography often are not helpful, because most of these tumours are small. Magnetic resonance imaging (MRI) may yield better results. Selective percutaneous transhepatic venous sampling often helps localize an insulinoma to the head, body, or tail of the pancreas, and selective arteriography is also often helpful in localising insulin-secreting lesions. Octreotide scanning localises insulinomas in approximately 50% of cases.

Treatment⁸ :

Approach Considerations

The mainstay of therapy for hypoglycaemia is glucose. Other medications may be administered based on the underlying cause or the accompanying symptoms (not discussed here).

Fasting hypoglycaemia

Dietary therapy may be useful for improving symptoms in patients with fasting hypoglycaemia. Regular meals/snacks are preferred, especially at night, with complex carbohydrates. If dietary therapy is inadequate, medical care for patients with fasting hypoglycaemia may include intravenous (IV) glucose infusion. However, IV octreotide is useful for suppressing endogenous insulin secretion. Reactive hypoglycaemia does not require medical care. Because exercise burns carbohydrates and increases sensitivity to insulin, patients with fasting hypoglycaemia should avoid significant activity. However, patients with reactive hypoglycaemia often find that their symptoms improve after embarking on a regular exercise program. The definitive treatment for fasting hypoglycaemia caused by a tumour is surgical resection.

Reactive Hypoglycaemia:

For patients with reactive hypoglycaemia, initiate a restriction of refined carbohydrates. Patients should avoid simple sugars, increase the frequency of their meals, and reduce the size of their meals. Patients may require six small meals and 2-3 snacks per day. Increased protein and fibre in the meal may be beneficial. In many patients, the use of alpha-glucosidase inhibitors (acarbose and miglitol) may help. These medications cause reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. This enzyme inhibition results in delayed glucose absorption and a lowering of postprandial hyperglycaemia and thus may prevent reactive hypoglycaemia.

Treatment of hypoglycaemia is by eating foods high in simple sugars or taking dextrose. If a person is not able to take food by mouth, an injection of glucagon may help. The treatment of hypoglycaemia unrelated to diabetes includes treating the underlying problem as well and a healthy diet. The term “hypoglycaemia” is sometimes incorrectly used to refer to the idiopathic postprandial syndrome, a controversial condition with similar symptoms that occur following eating but with normal blood sugar levels.

Medication Summary

The mainstay of therapy for hypoglycaemia is glucose. Other medications may be administered based on the underlying cause or the accompanying symptoms; however, these medications are not addressed in this article.

Glucose Supplement Class Summary: Glucose supplements are used to raise the patient’s serum glucose. Dextrose (Glucose-D)

Dextrose is a monosaccharide absorbed from the intestine and distributed, stored, and used by tissues. Parenterally injected, dextrose is used in patients unable to obtain adequate oral (PO) intake. Direct oral absorption results in rapid increases in blood glucose concentrations. Dextrose is useful in small doses, and there is no evidence that it may cause toxicity. Concentrated dextrose infusions provide higher amounts of glucose and increased caloric intake with minimum fluid volume. Its cause dictates the long-term management of hypoglycemia (e.g., insulinoma).

Dosage Forms & Strengths in treatment of “Hypoglycaemia.”

IV: 10-25 g (i.e. 20-50 mL 50% solution or 40-100 mL of 25%)

PO: 4-20 g as a single dose; may repeat after 15 min if self-monitoring of blood glucose shows continued hypoglycaemia.

A reminder used by the American Diabetes Association and others is the “rule of 15” – consuming 15 grams of carbohydrate followed by a 15-minute wait, repeated if glucose remains low (variable by individual, sometimes 70 mg/dL)^8,9.

A person can have severe effects of hypoglycaemia such that he cannot (due to combativeness) or should not (due to seizures or unconsciousness) be given anything by mouth. Medical personnel such as paramedics, or in-hospital personnel can establish IV access and give intravenous dextrose, concentrations varying depending on age (infants are given 2 ml/kg dextrose 10%, children are given dextrose 25%, and adults are given dextrose 50%). Care must be taken in giving these solutions because they can cause skin necrosis if the IV infiltrated, sclerosis of veins, and many other fluid and electrolyte disturbances if administered incorrectly. If IV access cannot be established, the patient can be given 1 to 2 milligrams of glucagon in an intramuscular injection.

If a person has less severe effects and is conscious with the ability to swallow, medical personnel may administer oral glucose. One situation where starch may be less effective than glucose or sucrose is when a person is taking acarbose. Since acarbose and other alpha-glucosidase inhibitors prevent starch and other sugars from being broken down into monosaccharides that can be absorbed by the body, patients taking these medications should consume monosaccharide-containing foods such as glucose tablets, honey, or juice to reverse hypoglycaemia.

Glycaemic Targets and Management of Hypoglycaemia:

Glycaemic management is primarily evaluated with Alc test, which is an important tool for evaluating glycaemic control and has substantial predictive value for diabetes complications. Alc demonstrates average glycemia over -3 months.⁵

Alc glycaemic goals

A1c testing should be performed routinely in all patients with diabetes at initial assessment and as part of continuing care^15.

• AI c goal for non-pregnant adults is <7% (53 mmol/l. (A)¹⁵

• Healthcare professionals may suggest stringent Alc goals [e.g. <6.5%(48 mmol/l] for selected patients if this can be achieved without substantial hypoglycaemia or other adverse effects of treatment (i.e., polypharmacy). Appropriate patients for this strategy might include those with short duration of diabetes. T2D treated with lifestyle or metformin only, long life expectancy, or no significant CVD. (C)¹⁵

• Less stringent Alcogels [e.g. <8% (64 mmol/l)] may be suggested in patients with a history of severe hypoglycaemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions. or long-standing diabetes in whom the AI c goal is challenging to achieve, despite diabetes self-management education. Proper glucose monitoring and effective doses of multiple glucose-lowering agents (including insulin). (B).¹⁵

• Reassessment of glycaemic targets over time is suggested based on the criteria demonstrated in Figure 2 or older adults.¹⁵

Hypoglycaemia: The limiting factor in glycaemic management

Hypoglycemia is the critical limiting factor for the glycemic management in patients with both TID and T2D1¹⁵.

• At each encounter, individuals at risk for hypoglycemia should be asked regarding symptomatic and asymptomatic hypoglycemia. (C)15

• For the conscious patient with blood glucose<70 mg/dl(3.9 mmol/L), glucose (15 20g) the preferred treatment, although any form of carbohydrate that contains glucose may be used. If self-monitoring of blood glucose (SMBG continues to demonstrate hypoglycemia. Fifteen minutes after the treatment, the treatment should be repeated. An individual should consume a meal or snack to prevent recurrence of hypoglycemia once SMBG returns to normal. (E)¹⁵

Prevention^9,10:

Among people with diabetes, prevention is by matching the foods eaten with the amount of exercise and the medications used. When people feel their blood sugar is low, testing with a glucose monitor is recommended. Some people have a few initial symptoms of low blood sugar, and frequent routine testing in this group is recommended. Emergencies are random but essential events in the lives of patients with diabetes. A significant source of morbidity and mortality, most emergencies are preventable by educating patients and their attendants, although some will still occur. Several causes are possible for the occurrence of stupor or coma in patients with diabetes. The most likely is hypoglycaemia, but the most serious prognostically is hyperglycaemia is imperative that diagnosis made as soon as possible-first, because hypo glycaemia coma responds promptly to simple therapy and second, because it is urgent that correct therapy instituted saves the individuals from the crisis.

CONCLUSION:

In old type 2 diabetes, treatment of hypoglycaemia has to be integrated into global and individualized care. Geriatric assessment in addition to avoiding lethal complications of diabetes, the prevention of decrease in the level of functional independence is the primary goal of this care and implemented by taking into account the type of patient, vigorous or frail. For the dependent elderly patient, maintaining comfort becomes the priority goal. From this assessment ensure the therapeutic and glycaemic goals. The choice of therapeutic tools is a function of fixed goals, of comorbidities, of the organization of care at home or in nursing homes, and the iatrogenic risk, in particular, the undernutrition and the hypoglycaemia.

Older patients with type 2 diabetes are at a higher risk of developing cognitive impairment and, therefore, are in danger of being unable to self-manage their disease. To prevent further complications from type 2 diabetes, patients can self-manage their glucose levels and medication intake. However, older patients who have had diabetes for a more extended period may experience memory loss and other cognitive dysfunctions, which can hinder their ability to manage their disease properly. “Older people with type 2 diabetes are at increased risk for cognitive dysfunction.” “Changes in cognition may negatively affect diabetes self-management behaviours, influencing self-care outcomes. The development of referral criteria, modes of rapid assessment, joint working practices and ‘outreach’ to all care settings and diagnostic groups are essential components of care of Hypoglycemic care.