Acute complications of diabetes mellitus: diagnostic criteria and treatment Assist. Prof. Svystun...

Acute complications of diabetes mellitus: diagnostic

criteria and treatment

Assist. Prof. Svystun I.I.

Classification of acute complications of DM

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Introduction Occur in both types of DM( type 1 and 2) Mortality rate in NKHHS is raging form 10~50%, depending on

underlying disease. Mortality rate in DKA is less than 5%. Thirteen medications and medication classes were implicated,

alone or in combination, in hospitalizations for adverse drug events. The four most commonly implicated — warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%) — accounted for an estimated two thirds of hospitalizations

An estimated 2–4% of deaths of people with type 1 diabetes have been attributed to hypoglycemia

Pathogenesis of DKAType 1 diabetes

Hyperglicemia

Osmotic diuresis

Volumen depletion Dehydration

Electrolite depletion

Initiating event

Insulin

Glucagon Protein catabolism

Amino acids

Gluconeogenesis

Lypolisis

Glycerol FFA´s

Ketogenesis

KetonemiaKetonuria

Acidosis

Precipitating factors:1) newly diagnosed diabetes (presenting manifestation);2) inadequate administration of exogenous insulin (inadequate

dose, insulin infusion catheter blockage, mechanical failure of insulin infusion pump);

3) increased requirements for insulin caused by the presence of an underlying stressful condition:

• an intercurrent infection (pneumonia, cholecyctitis);• a vascular disorder (myocardial infarction, stroke);• an endocrine disorder (hyperthyroidism,

pheochromocytoma);• trauma;• pregnancy;• surgery ;• medication (eg, corticosteroids, pentamidine, clozapine)4) Idiopathic (no identifiable cause)

Clinical presentation

Diabetic ketosis.

It is status which is characterized by increased level of ketones in blood, without clinical signs of dehydration and can be corrected by diet (fat restriction) and regular insulin injection.

DKA develops

over a period

of days or weeks.

Clinical presentation

nausea, vomiting abdominal pain palpitation

Rapid breathing flushed face dry tongue

Signs and symptoms.

Laboratory findings

Investigations1. A presumptive bedside diagnosis is justified if the

urine is strongly positive for both glucose and ketones.

2. Measurement of blood ß-hydroxybutyrate (ß -OHB) concentration, may not be available in all labs, besides, urine Ketone testing can be misleading due the following reasons:

• ◦ The used method does not detect the major ketone body B-hydroxybutyrate. (sodium nitroprusside only measures acetoacetate and acetone). Serum ß-OHB concentrations, may be increased to levels consistent with DKA when a urine ketone test is negative or shows only trace or small ketonuria

• ◦ The readings are qualitative depending on color comparisons

• ◦ High doses of Vitamin C may cause false-negative results, while some drugs may, on the other hand, give false-positive results.

Mild Moderate Severe

PG mg/dl >250 >250 >250

Arterial pH 7.25-7.3 7.0-7.24 <7.00

Serum HCO3 15-18 10 -15 <10

Urine Ketones positive positive positive

Serum ketones

positive positive positive

Effective SO(mOsm/kg)

variable variable variable

Anion gap >10 >12 >12

Mental status Alert alert/drowsy stupor/coma

Diagnostic Criteria

Treatment

The goals of therapy include:1.Reduction of hyperglycemia

2.Rehydratation

3.Correction of electrolyte imbalance

4. Correction of acid-base imbalance

5. Investigation of precipitating factors, treatment of complications.

6.Frequent patient monitoring

Fig. Management of adult patients with DKA. 2003 American Diabetes Association.

Chiasson J et al. CMAJ 2003;168:859-866©2003 by Canadian Medical Association

Nonketotic hyperglycemic-hyperosmolar state (NKHHS or HNS).

HNS is a syndrome characterized by impaired consciousness, sometimes accompanied by seizures, extreme dehydration, , and extreme hyperglycemia that is not accompanied by ketoacidosis.

The syndrome usually occurs in patients with type II DM, who are treated with a diet or oral hypoglycemic agents, sometimes it is a complication of previously undiagnosed or medically neglected DM (type II).

HNC usually develops after a period of symptomatic hyperglycemia in which fluid intake is inadequate to prevent extreme dehydration from the hyperglycemia-induced osmotic diuresis.

Predisposing factors

1. HNS seems to occur spontaneously in about 5 – 7 % of patients.2. Infection (e.g., pneumonia, urinary tract infection, gram-negative

sepsis) is underlying frequent precipitating cause.3. Use of certain drugs has been associated with this condition:• steroids increase glucogenesis and antagonize the action of

insulin;• potassium-wasting diuretics (hypokalemia decreases insulin

secretion), e.g., thiazides, furosemide;• other drugs, e.g., propranolol, azathioprine, diazoxide.5. Other medical conditions such as cerebrovascular accident,

subdural hematoma, acute pancreatitis, and severe burns have been associated with HNS.

6. Use of concentrated glucose solutions, such as used in peripheral hyperalimentation or renal dialysis, has been associated with HNC.

7. HNS can be induced by peritoneal or hemodialysis, tube feeding.

Clinical presentation

1. Polyuria, polydipsia, weight loss, weakness and progressive changes in state of consciousness from mental cloudiness to coma (present in 50 % of patients) occur over a number of days to weeks.

2. Because other underlying conditions (such as cerebrovascular accident and subdural hematoma) can coexist, other causes of coma should be kept in mind, especially in the elderly.

3. Seizures occur in 5 % of patients and may be either focal or generalized.

Physical examination

1. Severe dehydration is invariably present.

2. Various neurologic deficits (such as coma, transient hemiparesis, hyperreflexia, and generalized areflexia) are commonly present. Altered states of consciousness from lethargy to coma are observed.

3. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular disease) may be evident.

Laboratory findings

Laboratory findings

• Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. CMAJ April 1, 2003 vol. 168 no. 7 859-866

Laboratory findings

Treatment

This condition is a medical emergency and the patient should be placed in an intensive care unit.

Many of the management techniques recommended for a patient with DKA are applicable here as well.

The goals of therapy include:• rehydration;

• reduction of hyperglycemia;

• electrolytes replacement;

• investigation of precipitating factors, treatment of complications.

Diabetes Care January 2004 vol. 27 no. suppl 1 s94-s102

Lactic acidosis (LA)

DM is one of the major causes of LA, a serious condition characterized by excessive accumulation of lactic acid and metabolic acidosis.

The hallmark of LA is the presence of tissue hypoxemia, which leads to enhanced anaerobic glycolysis and to increased lactic acid formation.

The normal blood lactic acid concentration is 1mmol/l, and the pyruvic to lactic ratio is 10:1. An increase in lactic acid without concomitant rise in pyruvate leads to LA of clinical importance.

Pathogenesis

1. Heart and pulmonary failure (which leads to hypoxia).

2. Usage of bigyanids.

3. Alcohol intoxication.

4. Ketoacidosis (it is important to have a very high index of suspection with respect to presence of LA).

Predisposing factors

Metformin-Associated Lactic Acidosis

• Incidence:

0.03 cases/1,000 patient-years

• Mortality:

about 50% of cases• Sign and symptoms:

non-specific (nausea, vomiting, altered consciousness, fatigue, abdominal pain, and thirst)

1.Gowardman JR. Fatal metformin induced lactic acidosis: case report. N Z Med J 1995;108:230-11.2.Gan SC, Barr J, Arieff AI, Pearl RG. Biguanide-associated lactic acidosis. Case report and review of the literature. Arch Intern Med 1992;152:2333-6. 3.Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-9.4.Lee AJ. Metformin in noninsulin-dependent diabetes mellitus. Pharmacotherapy 1996;16:327-51.

Clinical presentation

Physical examination

1. Acrocyanosis is common.2. Tachycardia frequently is present, blood pressure

is decreased.3. Poor skin tugor and dry skin may be prominent.4. Hypothermia is common in LA.5. Hyperpnea or Kussmaul respiration are present

and related to degree of acidosis.6. Findings associated with coexisting medical

problems (e.g., renal disease, cardiovascular disease) may be evident.

Laboratory findings

1. Blood glucose level is not high

2. Glucosurea is absent.

3. Blood lactic acid is high.

Treatment of LA

LA is treated by correcting the underlying cause.Oxygentherapy Metylen blue (50 – 100 ml of 1 % solution i/v droply)Sodium bicarbonate therapy should be usedLA can be treated with low dose insulin regimens with 5 %

glucose solution infusion. Symptomatic therapy:- Hydrocortisone (250 mg i/v)- Unitiol (5% solution 10 ml i/v (1- 2 ml/10 kg)- α-lipoid acid (tioctic acid)- thiamine (its deficiency may be associated with

cardiovascular compromise and lactic acidosis. The response to thiamine repletion (given as 50-100 mg intravenously [IV] followed by 50 mg/d orally [PO] for 1-2 wk) may be dramatic and potentially lifesaving).

Sodium bicarbonate• The starting dose of sodium bicarbonate (NaHCO3

-) is one third to one half of the calculated extracellular bicarbonate (HCO3

-) deficit, as illustrated by the following formula:

HCO3 deficit (in mEq) = 0.5 × (Wt in kg) × (Desired HCO3 – Measured HCO3)

• Metabolic alkalosis can ensue after bicarbonate administration if the correction is complete rather than partial. This result can be avoided by titration of the bicarbonate dose to modest therapeutic end points (eg, arterial pH of 7.20).

• Because of increased CO2 production, sodium bicarbonate may precipitate ventilatory failure and, as such, must be given with caution.

Comparison of DCA, HNC and LA.

Hypoglycemia

It is a syndrome characterized by symptoms of sympathetic nervous system stimulation or central nervous system dysfunction that are provoked by an abnormally low plasma glucose level.

Hypoglycemia represents insulin excess and it can occur at any time.

Causes:

1. complication of treatment of diabetes mellitus with insulin or oral medications,

2. excessive insulin produced in the body (hyperinsulinemia),

3. inborn error of metabolism,4. medications and poisons,5. alcohol,6. hormone deficiencies,7. prolonged starvation, 8. alterations of metabolism associated with

infection, and organ failure.

Risk factors for hypoglycemiain diabetes (ADA, 2009)

www.uspharmacist.com: Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94:709-728.

Patophysiology

Clinical presentation

1. adrenergic symptoms (they are attributed to increased sympathetic activity and epinephrine release):

- sweating, - nervousness, - faintness, - palpitation- sometimes hunger;

2. cerebral nervous system manifestations: confusion, inappropriate behavior (which can be mistaken for inebriation); visual disturbances, stupor, coma or seizures. (Improvement in the cerebral nervous system manifestations will be with a rise in blood glucose.)

A common symptom of hypoglycemia is the early morning headache, which is usually present when the patient awakes.

Patients should be familiar with the symptoms of the hypoglycemia but some of them are not heralded by symptoms.

Physical examination

1. The skin is cold, moist.

2. Hyperreflexia can be elicited.

3. Hypoglycemic coma is commonly associated with abnormally low body temperature

4. Patient may be unconsciousness.

Laboratory findings

1. Low level of blood glucose• It is suggested that persons with diabetes

become concerned about the possibility of developing hypoglycemia when the self-monitored blood glucose concentration is falling rapidly or is no greater than 70 mg/dl (3.9 mmol/liter) (An Endocrine Society Clinical

Practice Guideline, 2009)

Treatment

Insulin–treated patients are advised

to carry sugar lumps, candy, or glucose tablets at all time.

Asymptomatic or mild-to moderate symptomatic hypoglycemia are effectively self-treated by ingestion of glucose tablets or carbohydrate-containing juice, soft drinks, milk, candy, other snacks, or a meal. Patients have to teach their family members to give such treatment if they suddenly exhibit confusion or inappropriate behavior.

• A commonly recommended dose of glucose in adults is 20 g. Clinical improvement should occur in 15–20 min.

Treatment• Parenteral treatment is necessary when a hypoglycemic

patient is unwilling (because of neuroglycopenia) or unable to take carbohydrate orally.

• Glucagon 1.0 mg in adults by an associate of the patient s/c, i/m. Although glucagon can be administered iv by medical

personnel, in that setting the standard parenteral therapy is iv glucose. If the patient does not respond to 1 unit of glucagon within 25 minutes, further injections are unlikely to be effective, and are not recommended;

Treatment• A standard initial glucose dose is

25 g. The glycemic response to iv glucose is, of course, transient.

• an i/v injection of 20 or 100 ml of 40-50 % glucose, followed by a continuous infusion of 5 % glucose (10 % glucose may be needed) until it clearly can be stopped safely;

• Food should be provided orally as soon as the patient is able to ingest it safely.

• glucocorticoids and adrenaline are helpful as well.• Octreotide has been used to treat sulfonylurea-

induced hypoglycemia

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