19.7 Acute Metabolic Complications

19.7.1 Diabetic Ketoacidosis

It is an acute metabolic complication of diabetes mellitus that may present with a decreased level of consciousness

Symptoms

• Nausea/vomiting
• Thirst/polyuria
• Abdominal pain
• Dehydration
• Shortness of breath
• Fruity smelling breath
• Fever
• Lethargy
• Obtundation/drowsiness
• Confusion
• Altered mental function
• Coma

Note:

• When you suspect DKA, confirm diagnosis immediately.
• All patients minimum should be admitted in hospital for intensive management.

Diagnostic Criteria

• Blood glucose > 11.0mmol/L or known diabetes mellitus
• Ketonuria ++ or more on Ketostix
• Glasgow Coma Scale less than 12, systolic BP below 90mmHg and pulse over 100 or below 60bpm each indicate severe status.

Investigations

• Check blood glucose
• Urine for ketones
• Arterial blood gases
• Urea, creatinine and electrolyte

Non-Pharmacological Treatment

• Admit for intensive care
• Insert nasogastric tube for gastric decompression
• Use DKA chart to guide treatment and monitor the patient

Pharmacological Treatment

Fluid and electrolytes replacement

If systolic BP < 90mmHg give:
A: 0.9% sodium chloride solution (500ml) over 10–15 minutes. If SBP remains below 90mmHg this may be repeated once. Most patients require between 500 to 1000ml given rapidly.

• If systolic BP remains <90mmHg consider other causes (septic shock, heart failure)
• Do NOT use plasma expanders

If the systolic BP is > 90mmHg
A: Normal Saline(NS) 1 litre + Potassium chloride (KCl) 2g when available 2 hourly for 1^st 4hours, then 4 hourly
OR
A: Ringer’s Solution 1 litre 2hourly for 1^st 4hours, then 4 hourly

• When blood glucose falls to 14 mmol/L or below, start 5% Dextrose 500mls 4hourly
• Isotonic dextrose saline may be used in place of dextrose 5%
• If a patient is still dehydrated continue Normal saline or Ringer’s solution as well.
• More cautious fluid replacement should be considered in young people aged 18–25 years, elderly, pregnant, heart or renal failure, mild DKA, other serious co-morbidities

Insulin Therapy
B: Soluble insulin 8 IU (0.1 IU/kg) IM and 8 IU IV at begining. Then give 8 IU (0.1 IU/kg) IM soluble insulin bolus hourly

• Check blood glucose 2hourly if using IM route or 4 hourly if sc route
• Expect a fall in capillary blood glucose of 3.0mmol/L/hour: increase the insulin rate by 1.0 IU/hour increments hourly until glucose falls at this rate.
• If blood glucose is fluctuating widely, then use the guide in Table 2:
• When blood glucose falls to 14 mmol/L or bellow give soluble insulin 4 IU SC 4 hourly OR IM 2 hourly and continue until the patient is able to eat again then change to twice or thrice daily insulin as follows:
  • Give insulin 0.5–0.75 IU/kg/day (the higher doses for the more insulin resistant i.e. teens, obese)
  • Give 50% of total dose with the evening meal in the form of long-acting insulin and divide remaining dose equally between pre-breakfast, pre-lunch and pre-evening meal.
    OR
  • Use pre-mixed insulin: give two thirds of the total daily dose at breakfast, with the remaining third given with the evening meal.

Table 19.5: Treatment of diabetic ketoacidosis in case of blood glucose fluctuations

Blood glucose mmol/L	Insulin 4 hourly sc OR 2hourly IM	5% dextrose 4hourly
>14.0	12	500ml
7.2–14.0	8	500ml
2.5–7.2	4	500ml
<25	4	100ml

Other important notes and measures

• Assess Cardial Vascular System (CVS) for volume overload (Input output chart, oedema (lungs, peripheral)
• Maintain an accurate fluid balance chart, the minimum urine output should be no less than 0.5ml/kg/hour
• Consider urinary catheter if no urine passed after 2 hours or if incontinent
• Consider nasogastric tube and aspiration if the patient does not respond to commands
• Screen for infection and give antibiotics if clinical evidence of infection.
• Only with severe acidosis Sodium bicarbonate (NaHCO3) 50mmol may be given under doctor’s instruction.

Table 19.6: Diabetes ketoacidosis initial management chart

Name of Patient:								Reg. Ward:		No.:
Hour	Time	Soluble Insulin	IV Fluids		Blood glucose	Urine		Electrolytes		Remarks
						Glucose	Ketones
			When KCL Available	When No KCL				Na+	K+
1st		8IU IV 8IU IM	2 Litres N/S	2 Litres N/S
2nd		8IU IM	1 Litre N/S +2g KCL	Darrow’s 1 Litre
3rd		8IU IM	↓	↓
4th		8IU IM	1 Litre N/S + 2g KCL	Darrow’s 1 Litre
5th		8IU IM	↓	↓
6th
7th
8th
9th
10th
11th
12th
13th
14th
15th
16th
17th
18th
19th
20th
21st
22n d
23r d
24th
Notes:
1. When Blood glucose falls to 14mmol/l (250mg/dl) or below Give soluble insulin 8IU (0.1IU/kg) SC 4 hourly OR im 2hourly Start 5% dextrose 500ml 4hourly
	If patient still dehydrated continue N/S OR Darrow’s solution as well Check blood glucose 2hourly if using IM route OR 4 hourly if using SC route Blood Glucose Insulin 4 hourly OR 2 hourly IM SC 4 hourly 5% Dextrose mmol/l mg/dl >14.0 >250 12 500 ml 7.2–14.0 130–250 8 500 ml 2.5–7.2 45–130 4 500 ml <2.5 <45 4 1000 ml
2.	Potassium chloride should be mixed in N/S. If not available use Darrow’s Solution as shown
3.	With severe acidosis, NaHCO3 50mmol should be given under doctor’s instruction
4.	Isotonic dextrose/saline can be used in place of 5% dextrose
5.	Patient should remain under close observation

19.7.2 Non-ketotic hyperosmolar state (NKHS)

It is a serious condition most frequently seen in older persons with T2DM. In NKHS, blood sugar level rise and the body tries to get rid of the excess sugar by passing into urine.

Diagnostic Criteria

• Polyuria
• Ortostatic hypotension
• Altered mental state lethargy, obtundation, confusion
• Seizures, possible coma
• Diminished oral intake of fluids
• Profound dehydration
• Hypotension
• Tachycardia
• Weight loss

Differentiated from DKA by no nausea and vomiting, no abdominal pain, and no Kussmaul breathing

Note: Try to identify precipitating factors: • Poor oral fluid intake • MI, stroke, sepsis, pneumonia and other serious infections • Medicines: thiazides diuretic, glucocorticoids, phenytoin

Laboratory investigation

• Blood glucose
• Serum electrolytes (K+, Na+, Cl–)
• Initial serum K+ may be falsely high due to extracellular shifts.
• Renal function (Urea and Creatinine)
• Serum osmolarity (usually >330 mosmol/L)
  • Serum osmolarity = 2(Na⁺+ K⁺) + glucose + Urea (Glucose and Urea in mmol/L)
  • Normal is < 310 mosmol/L as calculated

Note:

• A patient may be acidotic due to lactic acidosis or shock/sepsis: in this case principle management as in case of DKA
• IV fluids should be replaced as half-normal saline (0.45%) if hypernatremia, normal saline if serum sodium is normal
• There is frequently intercurrent illness usually sepsis, CVA, or cardiac and these must be diagnosed and treated.

19.7.3 Diabetes and other cardiovascular diseases

Diabetic patients are 2–4 times likely to develop cardiovascular diseases mainly due to atherosclerosis and hypertension.

The clinical spectrum of cardiovascular diseases includes:

• Coronary heart disease
• Angina (which may be silent)
• Acute coronary artery syndrome
• Congestive cardiac failure
• Sudden death
• Cerebral vascular accident (stroke, transient ischaemic attacks and dementia)
• Peripheral vascular disease (intermittent claudication, foot ulcer and gangrene).

Assessment (annual)

• ECG, Chest X-Ray, if with symptoms/signs of heart failure.
• Peripheral vascular disease evaluation includes doppler and angiography of lower limbs.

Pharmacological Treatment
Acute coronary syndrome

• All adults with T2DM and recent acute coronary syndrome and/or coronary stent should receive dual anti-platelet therapy, for 12 months after the event or procedure:
  A: Low-dose aspirin (75–100 mg daily)
  AND
  D: Clopidogrel (75mg daily)

• Aspirin is also indicated for primary prevention for people with T2DM over the age of 40 years with family history of ischaemic heart disease (IHD), cigarette smooking, obesity, proteinuria or dyslipidemia.
• It is contraindicated in peptic/duodenal ulcer, dyspepsia, hurtburn, malignant hypertension, haemorrhagic stroke.

Hyperlipidaemia

• Statin therapy results in a significant decrease in CVD morbidity and mortality in T2DM for those at high CVD risk.
  B: Simvastatin 20mg daily. Dose may be increased to 40mg daily if required
  OR
  B: Atorvastatin 10mg daily. Dose may be increased to 80mg daily if required

• Fenofibrate reduces incidence of retinopathy and need for laser surgery, peripheral neuropathy and improvement in proteinuria, sugesting a more generalsed effect on microvascular disease independent of dyslipidaemia Fibrates
• Shouldbe used in mixed hyperlipidemias which have not responded adequately to diet or other therapy.
• Are more effective in lowering triglycerides and increasing HDL, but less effective in lowering cholesterol.
• Should be used with caution in combination with statins.
• Can enhance the effects of warfarin and antidiabetic agents
• Are contraindicated in patients taking Orlistat.
  D: Fenofibrate 67–267mg/day
  OR
  D: Gemfibrozil 0.9–1.2g/day

19.7.3.1 Hypertension

In people with T2DM, antihypertensive therapy with an angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI) decreases the rate of progression of albuminuria, promotes regression to normal albuminuria and may reduce the risk of decline in renal function. Therefore:

• BP-lowering therapy in people with diabetes should preferentially include an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) e.g:
  C: Enalapril: 10 mg–40 mg orally daily, taken either as a single dose or two divided doses (enalapril 5 mg–10 mg twice a day)
  C: Losartan: Initial dose: 50 mg orally once a day. Maintenance dose: 25–100 mg orally per day in 1 or 2 divided doses

• The target level for optimum BP is controversial. It is reasonable to target BP levels of <140/90 mmHg for people with diabetes, with lower targets for younger people and those at high risk of stroke. The target BP for people with diabetes and microalbuminuria or proteinuria remains <130/80 mmHg.
• Combining an ARB and an ACEI is not recommended.
• If monotherapy does not sufficiently reduce blood pressure (BP) add one of the following:
  • Calcium channel blocker:
    C: Amlodipine 5–10mg once daily
  • Low-dose thiazide or thiazide-like diuretic:
    A: Bendrofluazide 5mg once daily

• ACE-inhibitors and ARBs should be stopped pre-conception. Diltiazem in extended release forms may be a useful substitute.

19.7.3.2 Diabetic Peripheral Neuropathy

All patients should be screened for distal symmetric polyneuropathy starting at diagnosis of T2DM and at least annually thereafter.

Diagnostic Criteria

• Unsteady gait
• Burning, aching pain or tenderness in legs or feet (occurring at rest or at night, not related to exercise)
• Prickling sensations in legs and feet (occurring at rest or at night, distal>proximal, stocking glove distribution)
• Numbness in legs or feet (distal>proximal, stocking glove distribution)
• History of previous foot ulceration and/or amputation.

Investigations
Test for:

• Sensation (10g monofilament or cotton wool)
• Vibration (128 Hz tuning fork)
• Postural hypotension and pulse (tibial and dorsalis)
• Inspect foot for structural abnormalities and ulceration.

Pharmacological Treatment

Burning pain: Antidepressants:

C: Imipramine – 50–150mg/day

OR

A: Amitriptyline – 75–150mg/day

 

Lancinating pain: Anticonvulsants:

A: Carbamezapine – 400–800mg/day

OR

C: Sodium valproate – 10–15 mg/kg/day)

Give foot care education and advice on appropriate footwear.

 

19.7.3.3 Diabetic Nephropathy

It is a progressive kidney disease that damages the capillaries in the kidney’ glomemeruli because of the long-lasting diabetes mellitus. People with diabetes and microalbuminuria have high cardiovascular disease risk, and should be treated with multifactorial interventions (refer to the section on CVD cardiovascular risk).

Diagnostic Criteria

• There are no symptoms in early stage
• In later stage, there is body swelling, most often feet and legs

Investigations

• Perform regular urine tests to check the albumin

Non-Pharmacological Treatment

Reduce salt intake (< 2g/day) and restrict proteins (<1g/kg/day)–explore options from patient’s dietary history.

Pharmacological treatment

C: Losartan: Initial dose: 50 mg orally once a day. Maintenance dose: 25–100 mg orally per day in 1 or 2 divided doses