2. Topics covered
• Definition of Diabetes Mellitus
• Acute metabolic complications of DM
• Diabetic ketoacidosis
• Hyperosmolar hyperglycaemic state
• Hypoglycemia
• Lactic acidosis
3. Definition of Diabetes Mellitus
Diabetes mellitus is characterized by chronic hyperglycemia
with disturbances of carbohydrate, fat, and protein
metabolism resulting from defects in insulin secretion, insulin
action, or both.
4. Etiologic Classification of Disorders of glycemia
• Type 1
β-cell destruction, usually leading to absolute insulin deficiency
Autoimmune
Idiopathic
• Type 2
may range from predominantly insulin resistance with
relative insulin deficiency to a predominantly secretory defect
with or without insulin resistance
5. Other Specific Types of Diabetes Mellitus
• Genetic defects of β-cell function
Maturity onset diabetes of young
(MODY)
• Endocrinopathies
Cushing syndrome
Acromegaly
Pheochromocytoma
Glucagonoma
Hyperthyroidism
• Other genetic syndromes associated
with diabetes
Down syndrome
Klinefelter syndrome
Prader-Willi syndrome
Turner syndrome
Wolfram syndrome
7. Acute Metabolic Complications Of Diabetes Mellitus
• Diabetic ketoacidosis
• Hyperosmolar hyperglycemic state
• Lactic acidosis
• Hypoglycemia
8.
9. Diabetic ketoacidosis
DKA is defined as the presence of all three of the following:
(i) hyperglycemia (glucose >250 mg/dL),
(ii) ketosis (≥ 3.0 mmol/L)
(iii) acidemia (pH <7.3)
11. • Normally, ketone bodies increase insulin release from the pancreas;
the insulin in turn suppresses ketogenesis.
• In the insulin-deficient state, the pancreatic β-cells are unable to
respond, and ketogenesis proceeds unchecked.
• Ketolysis occurs in the mitochondria of organs, which can use ketone
bodies as an alternative energy source.
• Ketone bodies provide an important source of energy for the central
nervous system during periods of starvation.
12. Precipitating factors
• Infection --20% to 40%
Most common infection involving urinary tract and lungs
• Cerebrovascular accident
• Myocardial infarction
• Pancreatitis
• Alcohol abuse
• Drugs (steroids, dobutamine, terbutaline,thiazides, antipsychotics
such as clozapine, olanzapine, and risperidone ,interferon-α ,ribavirin,
cocaine etc.. )
• Omission of insulin
• Pregnancy
13. Symptoms
• polyuria and polydipsia.
• weight loss.
• Nausea and vomiting,
• increasing malaise and loss of
appetite
• Dehydration
• Abdominal pain
• Leg cramps
• Blurring of vision
• Fever
• h/o cough and urinary tract
infection
• degrees of change in mental
status, ranging from drowsiness
• to stupor to coma.
14. Signs
• Dehydration
• Hypotension (postural or supine)
• Cold extremities/peripheral cyanosis
• Tachycardia
• Air hunger– kussumauls breathing
• Fruity odour ( as acetone is excreted from lungs )
• Hypothermia
• Delirium, drowsiness, coma(10%)
15. Initial Evaluation of the Patient with Suspected Diabetic
Ketoacidosis
• History of diabetes, medications, and symptoms
• History of diabetes-related complications
• Utilization of medications
• Social and medical history (including alcohol use)
• Vomiting and ability to take fluids by mouth
• Identify precipitating event leading to elevated glucose (pregnancy, infection,
omission of insulin, myocardial infarction, central nervous system event)
• Assess hemodynamic status
• Examine for presence of infection
• Assess volume status and degree of dehydration
• Assess presence of ketonemia and acid–base disturbance
17. Indicators of severe diabetic ketoacidosis
• Blood ketones > 6 mmol/L
• Bicarbonate < 5 mmol/L
• arterial pH < 7.0
• Hypokalaemia on admission (< 3.5 mmol/L)
• Glasgow Coma Scale score < 12
• O2 saturation < 92% on room air
• Systolic blood pressure < 90 mmHg
• Heart rate > 100 or < 60 beats per minute
• Anion gap > 16 mmol/L
18. Investigations
• Venous blood for urea, electrolytes, glucose, bicarbonate and acid–
base status (venous blood can be used in portable and fixed blood gas
analysers, and differences between venous and arterial pH and
bicarbonate are minor).
• Urine or blood analysis for ketones
• Electrocardiogram (ECG).
• Infection screen: full blood count, blood and urine culture, C-reactive
protein, chest X-ray. Although leucocytosis invariably occurs in DKA,
this represents a stress response and does not necessarily indicate
Infection.
20. Fluid replacement
Administer Normal saline as indicated to maintain hemodynamic status, then
follow general guidelines:
• NS for first 4 hr.
• Consider half NS thereafter.
• Change to D5 half NS when blood glucose ≤250 mg/dL.
21. Insulin
• Regular insulin 10 U i.v. stat (for adults) or 0.15 U/kg i.v. stat.
Start regular insulin infusion 0.1 U/kg per hour or 5 U per hour.
• Increase insulin by 1 U per hour every 1–2 hr if less than 10%
decrease in glucose or no improvement in acid–base status.
• Decrease insulin by 1–2 U per hour (0.05–0.1 U/kg per hour) when
glucose ≤250 mg/dL and/or progressive improvement in clinical status
with decrease in glucose of >75 mg/dL per hour.
• Do not decrease insulin infusion to <1 U per hour.
• Maintain glucose between 140 and 180 mg/dL.
22. Cntd..
• If blood sugar decreases to <80 mg/dL, stop insulin infusion for no
more than 1 hr and restart infusion.
• If glucose drops consistently to <100 mg/dL, change i.v. fluids to D10
to maintain blood glucose between 140 and 180 mg/dL.
• Once patient is able to eat, consider change to s.c. insulin:
Overlap short-acting insulin s.c. and continue i.v. infusion for 1–2 hr.
For patients with previous insulin dose: return to prior dose of insulin.
For patients with newly diagnosed diabetes: full-dose s.c. insulin based
on 0.6 U/kg per day.
23. Potassium
• Do not administer potassium if serum potassium >5.5 mEq/L or patient is anuric.
• Use KCl but alternate with KPO4 if there is severe phosphate depletion and
patient is unable to take phosphate by mouth.
• Add i.v. potassium to each liter of fluid administered unless contraindicated.
24. Bicarbonate
• Adequate fluid and insulin replacement should resolve the acidosis
• If pH is <7.0, give 100 mL NaHCO3 over 45 min.
• Check acid–base status 30 min later and repeat if pH remains <7.0.
• Acidosis may reflect an adaptive response, improving oxygen
delivery to the tissues, and so excessive bicarbonate may induce
a paradoxical increase in cerebrospinal fluid acidosis and has
been implicated in the pathogenesis of cerebral oedema in
children and young adults.
• No studies to date have shown any benefit of bicarbonate therapy in
patients with DKA whose pH is between 6.9 and 7.1
25. Phosphate
• During treatment with insulin, phosphate is taken up intracellularly
with resultant hypophosphatemia. Hypophosphatemia is associated
with a number of clinical sequelae, including decreased cardiac
output, respiratory muscle weakness, rhabdomyolysis, central
nervous system depression, seizures and coma, acute renal failure,
and hemolysis.
• Intravenous phosphate therapy may lead to hypocalcemia. Thus, the
degree of phosphate replacement and type of phosphate treatment
required in DKA and HHS remain controversial.
26. • Phosphate replacement should be reserved for those with severe
hypophosphatemia of 1.5 mg/dL or less and in whom serum calcium
concentrations are normal.
• The use of small amounts of potassium phosphate with potassium
chloride given intravenously appears to be safe and effective.
• Oral phosphate repletion is always preferable to intravenous
repletion and should be commenced as soon as patients are able to
take food by mouth.
27. Ongoing monitoring
• Blood glucose should be checked hourly
• Electrolytes and acid–base status should be reviewed every 2 to 4
hours as indicated
• BUN and creatinine should be checked every 4 hours
• Use of a flow chart documenting clinical status (blood pressure, intake
and output of fluids, and level of consciousness if indicated), serum
glucose, electrolytes, and anion gap is recommended.
• If pneumonia is suspected and the initial chest radiograph shows no
evidence of consolidation, a repeat chest radiograph should be
performed after at least 4 L of fluid has been administered.
28. • Pregnancy testing should be considered for women of
reproductive age because of the potential deleterious
consequences of DKA and uncontrolled diabetes on fetal
well-being.
• Once the patient is able to tolerate oral fluids and start
eating, the shift from intravenous to subcutaneous insulin
should be undertaken.
• When changing to subcutaneous insulin, the intravenous
infusion of insulin should be continued for 1 to 2 hours after
the subcutaneous insulin has been administered, and the
dextrose infusion should be continued until the patient has
eaten a meal.
29. • Stopping the insulin infusion for more than 30 to 60 minutes
without administering short- or rapid-acting subcutaneous
insulin should be avoided because the half-life of intravenous
insulin is 2 to 4 minutes and ketoacidosis may recur rapidly in
the absence of exogenous insulin.
30.
31. Complications of DKA
• Shock
If not improving with fluids r/o MI
• vascular thrombosis
Severe dehydration
Cerebral vessels
Occurs hours to days after DKA
• Cerebral Edema
• First 24 hours
• Mental status changes
• May require intubation with
hyperventilation
• Pulmonary Edema and ARDS
Result of aggressive fluid resuscitation
• Hypoglycemia
• Hypokalemia
• Hypophosphatemia
• Hyperchloremic acidosis
• Hypocalcemia
32. Hyperosmolar Hyperglycemic State
• Life threatening emergency
• Less severe than DKA
• Previously known as Hyperosmolar hyperglycemic non ketotic coma.
• infection is the most common precipitating factor
• Characterised by
Hyperglycaemia
Hyperosmolar
Dehydration(fluid loss may be 10–12 L in a person weighing 100 kg).
Without ketoacidosis
33. Diagnostic criteria
• Plasma glucose >600mg/dl
• Arterial pH >7.30
• Serum bicarbonate >5mEq/L
• Serum ketone – small or negative
• Urine ketone- small or negative
• Effective serum osmolality- >320mOsm/kg
• Anion gap <12
• Mental status – stupor or coma .
35. Etiology
• Patient with T2DM prone to
develop it
• Old age
• Living alone, No access to
medical treatment
• Acute infection, burns, and
trauma
• CVA, MI
• Alcohol excess
• Recurrent vomiting/diarrhea.
• DRUGS: Thiazide ,Steroids,
Atypical antipsychotic,
Antiarrythmics, Antiepileptic,
Antihypertensive: CCB, Thiazide,
Diuretics
37. Signs
• Tachycardia
• Hypotension
• tachypnea
• hyperthermia/hypothermia
• head to toe examination for signs of dehydration
every 1L body fluids loss, there is 1kg of weight loss
skin turgor
dryness of skin
Dry, sticky mouth
Lethargy
38. Management
• Fluid replacement
Rapid infusion of large amount of fluid to correct circulation and to
reestablish adequate urine flow
Fluid deficit in HHS is 11-12L
Isotonic 0.9% saline is used - 2L within 2hour
Then change to 0.45% isotonic saline
When the glucose level approach normal after the hydration and insulin
therapy, then 5% dextrose is given as the vehicle for free water.
Fluid deficit should correct estimated deficit within 24 hour.
in patient with renal/cardiac compromise, CVP monitoring and serum
osmolality is mandatory while the infusion to avoid fluid overload.
39. Ctnd..
• Insulin therapy
• Regular insulin by continuous IV infusion is the treatment of choice.
• Exclude hypokalaemia
• IV bolus of regular insulin (0.15 u/kg)
• Followed by 0.1 u/kg/ hour
• Until blood glucose falls to 300mg/dl
• Then, reduce to 0.05 u/kg/hour plus 5% dextrose
• Target: blood glucose below 250mg/dl
• When the patient is conscious, ask to take orally for maintenance of blood
sugar.
40. • Potassium replacement
• Mild to moderate hypokalemia is not uncommon in HHS.
• Insulin therapy and volume expansion decreased the K+ concentration,
hence K+ replacement is needed.
• Once renal function is assured, K+ may be given to prevent hypokalemia
• When IV fluids infusion, monitor serum potassium level. When it falls below
5 mEq/L, and urine output is good, 20-30 mEq/L of postassium may be given.
• Treat the cause
41. Hypoglycemia
• The laboratory diagnosis of hypoglycemia is usually defined as a
plasma glucose level <2.5–2.8 mmol/L (<45–50 mg/dL), although the
absolute glucose level at which symptoms occur varies among
individuals.
• For this reason, Whipple’s triad should be present:
(1) symptoms consistent with hypoglycemia,
(2) a low plasma glucose concentration measured by a method capable of
accurately measuring low glucose levels (not a glucose monitor), and
(3) relief of symptoms after the plasma glucose level is raised.
47. Factitious Hypoglycaemia
• Most cases of factitious hypoglycemia are caused by the deliberate
administration of insulin or oral hypoglycemic agents by the patient,
although accidental administration or administration by a caregiver
may occur as well.
48. Hypoglycemia Due to Critical-Organ Failure
• Hepatic disease
Decreased Hepatic glycogenolysis and gluconeogenesis results in
hypoglycaemia. Causes are
toxic hepatitis
fulminant viral hepatitis
fatty liver or hepatitis associated with alcohol administration
cholangitis.
49. • Cardiac failure
The primary mechanism causing hypoglycemia in these patients is not known
but may be the combination of cachexia, lack of gluconeogenic substrate, and
liver dysfunction due to hepatic hypoxia and congestion.
• Renal failure
Renal insufficiency may be associated with hypoglycemia, particularly in
patients with end-stage renal disease.
The most common associated pathologies were
• Drug-induced hypoglycaemia- hypoglycemia as a result of decreased clearance of
hypoglycemic drugs or insulin
• Sepsis
• Severe malnutrition
50. Endocrine Deficiency Disorders and hypoglycaemia
• Glucagon and Catecholamine Deficiency
In clinical practice, isolated deficiency of glucagon and/or epinephrine in
patients without diabetes is extremely rare. There are very few case reports of
children with hypoglycemia that was presumed to be due to selective
deficiency of epinephrine or glucagon
• Growth-hormone And Cortisol Deficiencies
Cause -Hypopituitarism
Growth hormone and cortisol increase plasma levels of free fatty acids and
glycerol, resulting in suppression of glucose utilization and an increase in
gluconeogenesis. In addition, cortisol increases gluconeogenesis by induction of
hepatic gluconeogenic enzymes.
51. Immune Hypoglycemia
• Hypoglycemia Caused By Antibodies To Insulin
The antibodies may reduce the levels of free insulin Post injection, resulting in
higher postprandial levels of glucose, but may also increase the half-life of
insulin. Theoretically, a prolonged half-life of insulin causes late hypoglycemia
after a bolus injection of insulin.
• Hypoglycemia Caused By Antibodies To Insulin Receptor
• Most patients with hypoglycemia caused by antibodies to the insulin receptor
are women
• Hypoglycemia may be preceded by a phase of severe insulin resistance
associated with acanthosis nigricans and hyperglycemia in some patients,
whereas others present only with hypoglycemia.
52. Tumor-Associated Hypoglycemia
• Insulinoma
Insulin-producing islet-cell tumors occur with an incidence of 4 per 1 million
person-years.
The onset is usually insidious. About 94% of the tumors are sporadic, while
the rest occur as part of the multiple endocrine neoplasia type 1 syndrome.
• Non–islet Cell Tumor Hypoglycemia
Hypoglycemia may rarely occur in association with non–islet cell tumors. The
majority are large mesenchymal and epithelial tumors such as sarcoma,
mesothelioma, fibroma, hemangiopericytoma and hepatoma.
• Noninsulinoma, Pancreatogenous Hypoglycemia Syndrome
Nesidioblastosis
53. Reactive Hypoglycemia
• Alimentary Hypoglycemia
Alimentary hypoglycemia occurs in some patients after gastrectomy
with or without gastric drainage procedure and rarely in the absence of
gastrointestinal surgery.
• Reactive Hypoglycemia Associated With Early Diabetes Mellitus
Diabetic patients with reactive hypoglycemia usually have mild hyperglycemia
and develop symptoms of hypoglycemia 3 to 5 hours after a meal.
• Idiopathic Functional Hypoglycemia
54. Treatment
• Biochemical or symptomatic hypoglycaemia (self-treated)
• In UK, it is recommended that all glucose levels < 4.0 mmol/L (72 mg/dL)
are treated .People with diabetes who recognise developing hypoglycaemia
are encouraged to treat immediately. Options available include:
Oral fast-acting carbohydrate (10–15 g) is taken as glucose drink or tablets or
confectionery, e.g. 5–7 Dextrosol tablets (or 4–5 Glucotabs), 90–120 mL original
Lucozade, 150–200 mL pure fruit juice, 3–4 heaped teaspoons of sugar dissolved in
water)
Repeat capillary glucose measurement 1–15 mins later. If still < 4.0 mmol/L, repeat
above treatment
If blood glucose remains < 4.0 mmol/L after three cycles (30–45 mins), contact a
doctor. Consider glucagon 1 mg IM or 150–200 mL 10% glucose over 15 mins IV
Once blood glucose is > 4.0 mmol/L, take additional long-acting carbohydrate of
choice
Do not omit insulin injection if due but review regimen
55. • Severe (external help required)
This means individuals are either unconscious or unable to treat hypoglycaemia
themselves. Treatment is usually by a relative or by
paramedical or medical staff. Immediate treatment as below is needed.
• If patient is semiconscious or unconscious, parenteral treatment is required:
IV 75–100 mL 20% dextrose over 15 mins (= 15 g; give 0.2 g/kg in children) Or
IV 150–200 mL 10% dextrose over 15 mins Or
IM glucagon (1 mg; 0.5 mg in children) – may be less effective in patients on
sulphonylurea/under the influence of alcohol
• If patient is conscious and able to swallow:
Give oral refined glucose as drink or sweets (= 25 g) or 1.5–2 tubes of
Glucogel/Dextrogel Or Apply glucose gel or jam or honey to buccal mucosa
• Repeat blood glucose measurement after 10–15 mins and manage as per
biochemical hypoglycaemia
56. Lactic acidosis
• Normal plasma lactate: 0.5 to 1.5 meq/L.
• Lactic acidosis: plasma lactate concentration exceeds 4 to 5meq/L,
even among patients without a systemic acidosis
• The body tissues produce ~ 1500 mmol of lactate each day (15 to 30
mmol/kg per day)
• Metabolized mainly by the liver (Cori cycle)
• All tissues can produce lactate under anaerobic conditions.
57. Causes of Lactic Acidosis
The massively flawed Cohen-Woods classification
• Type A lactic acidosis:
impaired tissue oxygenation
• Shock: circulatory collapse
• Regional ischaemia
• Severe hypoxia
• Severe anaemia
• Carbon monoxide poisoning
• Type B1 lactic acidosis :
due to a disease state
• Malignancy
• Thiamine deficiency
• Ketoacidosis /HONK
• Septic shock
• Impaired hepatic or renal
clearance
58. • Type B2 drug-induced lactic
acidosis
Beta-2 adrenoceptor agonists-
Isoprenaline, adrenaline, salbutamol
Metformin
Isoniazid
Cyanide (and by extension
nitroprusside)
Xylitol, sorbitol, fructose
Propofol
The toxic alcohols eg. methanol
Paracetamol
Salicylates
NRTIs (nucleoside reverse
transcriptase inhibitors)
• Type B3 :
inborn errors of metabolism
• Numerous possible defects:
• Pyruvate dehydrogenase deficiency
• Electron transport chain enzyme
defects
• G6PD deficiency
59. • Mechanisms responsible for lactic acidosis in sepsis
• Endogenous catecholamine release and use of catecholamine inotropes
• Circulatory failure due to hypoxia and hypotension
• Microvascular shunting
• Inhibition of pyruvate dehydrogenase (PDH) by endotoxin
• Coexistent liver disease
• Slowed hepatic blood flow, impairing clearance
60. Symptoms
• exhaustion or extreme fatigue
• muscle cramps or pain
• body weakness
• overall feelings of physical discomfort
• abdominal pain or discomfort
• diarrhea
• decrease in appetite
• headache
• rapid heart rate
61. Treatment
• therapy with intravenous sodium bicarbonate for severe acidemia
(blood pH, <7.0)
• However, the value of bicarbonate therapy in reducing mortality or
improving hemodynamics remains unproven! Due to-
1.intracellular acidification due to the accumulation of carbon dioxide after
bicarbonate infusion and
2.a pH-dependent decrease in levels of ionized calcium, a modulator of cardiac
contractility
62. • Using dialysis to provide bicarbonate can prevent a decrease in
ionized calcium, prevent volume overload and hyperosmolality
(potential complications of bicarbonate infusion), and remove
substances associated with lactic acidosis, such as metformin.
• Continuous dialysis is often favored over intermittent dialysis
because it delivers bicarbonate at a lower rate and is associated with
fewer adverse events in patients with hemodynamic instability.
• Other buffers have been developed to minimize carbon dioxide
generation, including THAM (tris- hydroxymethyl aminomethane) and
Carbicarb (a 1:1 mixture of sodium carbonate and sodium
bicarbonate).
• Only THAM is currently available for clinical use!
63. • Potential Future Therapies
• The sodium–hydrogen (Na+–H+) exchanger NHE1 is activated during
lactic acidosis, leading to deleterious sodium and calcium overload in
the heart; its inhibition reduces cellular injury.
• NHE1 inhibitors attenuated the lactic acidosis and hypotension,
improved myocardial performance and tissue oxygen delivery,
enabled resuscitation, and reduced mortality in experimental models
of lactic acidosis.
