Diabetes

Investigations:
1. Urine glucose – using dipstick. Urine passed 1-2 hours after meal. Disadvantage – renal variation in
people and drugs affect these tests.
2. Blood glucose – capillary finger prick test. Cheap, quick, reliable. Venous plasma values are reliable.
Glucose: arterial > venous. Plasma > whole blood.
3. Interstitial glucose – using a sensor. Daily glucose profiles/night time glucose levels. However, not
more reliable than blood sugar.
4. Urine and blood ketones – ketonuria also is not diagnostic but ketonuria+glycosuria – highly likely
diabetes. Acetoacetate can be detected in urine by nitroprusside test buy not b-hydroxybutyrate – this
can be measured in blood.
5. Glycated hemoglobin – measure of glycemic control over weeks to months. Attachment (covalent) of
Hb to glucose increases amount in Hb1A1c fraction to relative non-glycated adult Hb (HbA0). These are
later separated by chromatography (rise of 11 mmol/mol in HbA1c = 2 mmol/L in blood glucose). But
HbA1c dec in anemia, pregnancy, uremia, hemoglobinopathy etc. (Hb1Ac reflects 2-3 months of
glycemia).
6. Islet autoantibodies – in patients with type 1 diabetes where there is autoimmune destruction of
pancreatic b-cells – these will be detected.
7. C-peptide – marker of endogenous insulin production (not exogenous). Hence, low – in long standing
type 1 diabetes. High – severe insulin resistance. Also used in diagnosis of severe hypoglycemia.
8. Urine protein – microalbuminuria or proteinuria in absence of UTI is indicator of diabetic nephropathy
and increased risk of macrovascular disease.

Diagnosis of Diabetes:
• Random plasma glucose/2 hours after 75g glucose blood > 11.1 mmol/L (200mg/dl).
• Fasting plasma glucose > 7.0 mmol/L (126 mg/dl).
• HbA1c > 48 mmol/mol
Diagnosis of pre-diabetes:
• Fasting plasma glucose is between > 6.1 mmol/L (110 mg/dl) and 7.0 (126mg/dl).
• 2 Hour glucose is 7.8-11.1 mmol/L (140-200).
• HbA1c UK: 42-47 mmol/mol
USA: 39-47 mmol/mol

Performing Oral Glucose Tolerance Test (OGTT):

Indications:
• Screening for gestational Diabetes.
• Patients who have low renal threshold for glucose.

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Procedure:
Prep: unrestricted carbohydrate diet for 3 days. Fasting overnight for atleast 8 hours. Rest for 30 minutes.
Remain seated for duration of test with no smoking. Sampling: measure plasma glucose before and 2 hours after
75g oral glucose drink.

Categories:
>normal >impaired(pre-diabetes) >diabetes
Diabetes: increased risk of microvascular complications.
Pre-diabetes: negligible risk of complications but increased risk of developing diabetes.
Stress hyperglycemia: hormones cortisol and catecholamines antagonise action of insulin-increased insulin
resistance.
Pregnant women with abnormal glucose tolerance should be urgently evaluated. Hb1Ac is NOT used to
diagnosed diabetes in pregnancy. After diagnosis confirmed, tests for plasma urea, creatinine, electrolytes,
lipids, liver, thyroid fts, blood/urine ketones and urine protein are performed.

1. Type 1 Diabetes
Insulin dependent Diabetes. Insulin deficiency (because autoimmune disorder – autoantibodies destroy b-cells
of pancreas) hence Insulin replacement is required. Age below 40. Weight loss. Polyuria. Polydipsia. Thirst.
Tetany. Vision Blurring. Glycosuria. Dehydration. Fatigue. Nocturia. Later tachycardia, hypotension,
unrestrained lipolysis, proteolysis, ultimately ketoacidosis. Patients present with short history of these
symptoms. Investigations as listed above.

2. Type 2 Diabetes
Diagnosis of exclusion. Non insulin dependent diabetes. Resistance to insulin action which enables b-cells to
make more insulin leading to increased levels of insulin initially. Later b-cells also aren’t able to produce
insulin. Relative insulin deficiency – insufficient insulin production to overcome resistance to its action. In
contrast to type 1, lipolysis and proteolysis are not unrestrained and weight loss and ketoacidosis seldom occurs.
Clinical features:
Age above 40. Obese. Symptoms from years (polydipsia, polyuria, lack of energy), vision Blurring.
Investigations: same as type 1.
Management:
Dietary therapy, exercise, less alcohol intake, drugs (metformin - 1st line treatment, sulphonylurea-
gliboxaamide). Antihypertensive drugs. ACEI.
Drug therapy: 1st line: metformin+sulphonylurea
2nd line: sulphonylurea+thiazolidinediones+DDP-4 inhibitors.
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3rd line: thiozolidinediones+DDP-4 inhibitors+ insulin+GLP-1 antagonist.

3. Hyperglycemia
Clinical features:
As listed above in type 1. Nausea, headache, hyperphagia, mood change, irritability, apathy, difficulty in
concentrating.
Investigations:
FBS, RBS, Hb1Ac, OGTT, dipstick urine, antibody test, serum fructosamine, electrolytes, creatinine,
proteinemia, CBC.
Management:
Dietary therapy, exercise, alcohol moderation, insulin.

Differentiation:
Diabetes type 1 Diabetes type 2
Onset <40 years >50 years
Duration Weeks Months to years
Body weight Normal/low Obese
Ketonuria Yes No
Rapid death without insulin Yes No
Autoantibodies Positive 80-90% Negative
Diabetic complications at No 25%
diagnosis
Family history of diabetes Uncommon Common
Other autoimmune disorders Common Uncommon

4. Hypoglycemia
Defined as blood glucose of less than 3.9 mmol/L (70mg/dl).
Causes: missed/delayed/inadequate meals, unexpected or unusual exercise, alcohol, errors in oral antidiabetic
agents, poorly designed insulin regimen, lipohypertrophy, malabsorption, Addison disease.
Clinical features:
History of hypoglycemic symptoms, fasting blood glucose 40 mg/dl or less, immediate recovery after
administering glucose – Whipples Traid. Person can collapse, pallor, confusion, speech difficulty, hunger,
sweating, cannot concentrate, trembling, pounding heart, anxiety, delirium, nausea, tiredness, headache.
There are two types: >nocturnal >exercise induced.
Management:

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If patient is conscious – oral glucose drink/sweets (apply glucose gel/jam/honey on buccal mucosa). If
patient is Unconscious- IV 75-100ml 20% dextrose over 15 minutes. IM glucagon 1mg. Repeat blood
glucose measurement after 10-15 minutes and manage. In case of severe hypoglycemia: 50ml of 50%
glucose IV. 1mg glucagon IM. Honey/syrup. Hypoglycemia caused by oral hypoglycemic agent: admitted
and observed.

5. Diabetic ketoacidosis
Characteristic of type 1 diabetes, presenting problem in newly diagnosed patients.
Mortality: cerebral edema (children and adolescents), hypokalemia, ARDS, MI, sepsis, pneumonia (adults).
Clinical features:
Hyperglycemia>250mg/dl. Metabolic acidosis (blood pH<7.3, serum bicarbonate<15meq/L),
hyperketonemia and ketonuria, urinary ketones positive, drowsiness, confusion, thirsty, abdominal pain,
rapid weak pulse, fruity smell in breath, hypothermia, nausea, vomiting, leg cramps, cold extremities,
high serum amylase.
Investigations:
Blood glucose, plasma osmolality, electrolytes, urinary ketones, ABGs, blood CP, xray chest, ECG,
urea/creatinine.
Management:
Hospital emergency. Fluid replacement (0.9% NaCl sol/normal saline) in first 2 hours. Regular/plain
insulin (IV/IM). Potassium replacement. Antibiotics (if infection). Monitor glucose hourly for 8 hours.
Monitor electrolytes every 2 hours. No use of bicarbonate/phosphate replacement. Go through table
20.16, page 737 of Davidson.
Complications: hypotension, cerebral edema, ARDS, thromboembolism, DIC, hypothermia, pulmonary edema.

6. Hyperosmolar State (hyperglycemic)

Emergency. Hypovolemia, hyperglycemia>600mg/dl. PH normal. Bicarb>15, dehydration, nausea, no
ketunuria, hyperosmolality glycosuria (loss of fluids/electrolytes). Rapid shifts in osmolality is avoided
(measured fluid replacement is done instead). 0.9% NaCl solution is initial treatment. Insulin later introduced
when rate of fall in blood glucose has plateaued.
Osmolality is measured by: 2[Na+]+[glucose]+[urea]
Normal value: 280-290 mmol/L. High>340 mmol/L.
Hyperosmolar NonKetotic Coma:
Clinical features:
Nausea, dehydration, severe hyperglycemia, hyperosmolarity, hyperketonemia absent, acidosis.
Investigations:

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Blood glucose>600mg/dl, serum osmolarity>320mOsm/kg, hypoketonemia, acidosis (pH<7.3).
Management:
Calculate serum osmolality frequently. Fluid replacement with 0.9%NaCl solution. Insulin IV Infusion.
Reduce glucose by no more than 5 mmol/hr. Give prophylactic anticoagulation. Assume high risk of foot
ulceration.

Drugs for Hypoglycemia: metformin (1st line treatment). If intolerant: metformin sulphonylureas (glimpiride
or glibencamide).
Following are all the drugs: >biguanides (metformin) >sulphonylureas >a-glucosidase inhibits
>thiazolidinediones >DPP-4 inhibitors >GLP-1 receptor agonists >SGLT2 inhibitors >insulin therapy.

7. Diabetes in pregnancy

• Control of established Diabetes before and during pregnancy.

• Gestational diabetes(inability to raise insulin secretion adequately to compensate for pregnancy induced
insulin resistance.
• Screen for GD (at high risk) by OGTT at 24-28 weeks, Hb1A1c, blood glucose.
Clinical features of GD:
Pregnant lady, weight loss, hyperglycemia.
Complications: inc rate of perinatal morbidity, neonatal morbidity, inc incidence of subsequent diabetes in
mother.
Treatment:
Diet modification, insulin, oral hypoglycemic drugs are contraindicated. Metformin or glibencamide can
be used if necessary.

8. Surgery and diabetes

Diabetics have 50% more perioperative mortalit than others. Surgery – induces stress and counter regulatory
hormones > S° inc in secretion of insulin > metabolic decompensation > DKA.
• Preoperative Assessment: if Surgery not urgent, control and risk factors assessed. Inc HbA1c usually
means adverse outcomes. Should be in range 64 and 75 mmol/mol (8% and 9%).
• Perioperative management: admitted.
• Post operative assessment: patients who need to fast after surgery should be maintained on IV insulin
and fluids until able to eat and drink. If dextrose Infusion is given along then also give saline and
potassium supplements. Then blood glucose should be maintained btw 150-180 mg/dl to optimise
wound healing. (Page 755, figure 20.19 Davidson).

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UQ: Complications of diabetes:
• Microvascular – retinopathy, nephropathy, neuropathy (peripheral/autonomic), foot disease
(ulceration, arthropathy).
• Macrovascular – coronary circulation(MI), cerebral circulation (transient ischemic attack,
stroke), peripheral circulation (ischemia, claudification).

9. Diabetic Retinopathy
Risk factors: long duration of Diabetes, poor glycemic control, hypertension, hyperlipidemia, pregnancy,
obesity, smoking.
Clinical features:
Dot blot Hemorrhage, cotton wool spots, microaneurysms, bright yellow coloured hard exudate,
loss/defect in vision, fibrosis.
Management:
Control hypertension, avoid smoking, good glycemic control, ophthalmoscopy, retinal photocoagulation,
argon laser photocoagulation, virectomy.
(Cataract: permanent lens opacity and is common cause of visual deterioration in elderly. Lens thickens and
opacifies with age. Snow flake cataract in young patients with poorly controlled diabetes).

10. Diabetic Nephropathy

Causes: Diabetic glomerulosclerosis, ischemic lesions, infective lesions.
Risk factors: poor glycemic control, long duration of diabetes, presence of other microvascular
complications, ethnicity (asians etc), preexisting HT, family history of diabetic nephropathy, family
history of hypertension.
Stages: microalbuminuria – progressive Diabetic nephropathy – renal failure.
Clinical features:
Periorbital puffiness, edema of feet, hypertension.
Investigations:
Urine dipstick (Microalbuminuria, ACR>300mg/mmol, macroalbuminuria – overt nephropathy), heavy
proteinuria, urine culture, ultrasound kidney, raised urea/creatinine.
(Screening type 1: annually from 5 years after diagnosis. Type 2: annually from time of diagnosis).
UQ: natural history of diabetic nephropathy: first few years of type 1 DM, hyperinfiltration which
declines to normal value at approx 10 years. After 10 years, there is sustained proteinuria and by approx
14 years, it reaches nephrotic range. Renal function continues to decline with endstage at 16 years.
Management:

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Aggressive decrease in BP. Aggressive decrease in CVS risk factors. Optimisation of glycemic control. 1st
line therapy – ACEI (captopril etc)/ARBS(losartan)/CCBs. 2nd line therapy – diuretic and/or salt
restriction. (Electrolytes and RFTs should be checked after starting these drugs.) Renal transplantation,
dialysis for end stage renal disease, reduce dosage of insulin, low protein diet.

11. Diabetic Neuropathy

Classification:
Clinical features:
Polyneuropathy Mononeuropathy Autonomic
(symmetrical/sensory)
• Paresthesia in • Mononeuropathy • Sympathetic/parasympathetic
feet and involves 1 nerve. nerves.
hands. • Motor/sensory • Postural hypotension.
• Dull pain in • Diplopia • Resting tachycardia.
lower limbs, • Carpal tunnel • Dysphagia.
worse at night. syndrome • Nocturnal diarrhea.
• Burning • Foot drop • Sweating on face during
sensation in • Mononeuritis eating.
sole. multiplex • Vomiting.
• Sense of • Impotence.
numbness in • Urinary incontinence.
feet. • Feet feel cold.
• Loss of tendon • Bullous formation.
reflexes in
• Decreased pupil size.
lower limbs.
• Loss of awareness of
• Glove and hypoglycemia.
stocking type
• Fixed HR.
impairment.
• Charcot joints.
• Less vibration.

Asymmetrical/Motor
• Diabetic
amyotrophy.
• Progressive
weakness of
muscles.
• Inc CSF
protein.
• Neuropathic
cachexia.
• Loss of tendon
reflexes.

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Management:
Strict glycemic control. Tricyclic antidepressants. Anticonvulsants. Antiarrythmics. Opiates (all these for
pain and paraesthesia). Support stocking, fludrocortisone, NSAIDs (all these for postural hypotension).
Metoclopromide (for gastroparesis). Loperamide (for diarrhea). Laxatives (for constipation).
Anticholinergic (for excessive sweating).

12. Diabetic Foot

Tissue necrosis due to hyperglycemia.
Causes: neuropathy, infection, ischemia.
Clinical features:
(Symptoms):Hyperglycemia, neuropathy, ischemia, paraesthesia, claudication, pain in calf muscles, rest
pain, numbness. (Structural damage): ulcer/wound, sepsis, abscess, Gangrene, osteomyelitis, charcot
joint/foot
(Charcot Foot: hot, red, swollen foot. Bone destruction- xray. Foot ulcer. Treat by immobilisation and avoid
weight on foot. Lasts 3-6 months. Remodelling of fractured fragments).
Management:
>P° prevention >treatment
Feet should be screened annually. Two simple tests to grade risk: 10g monofilament (sensation at 5 points
on each foot and foot pulses palpated). Removal of callus skin with scalpel.
Care: inspect feet everyday, wash feet everyday, moisturise skin if dry, change socks everyday, avoid
walking barefoot, don’t burst blisters, don’t attempt to remove callus/corn, avoid high/low temperatures,
specially manufactured orthotic footwear, ensure diabetic control, control edema, presentation is
necessary.
(Foot ulcer: debridement of dead tissue. Antibiotics. Pressure relief using customised insoles, specialised
orthotic footwear, total contact plaster, non removable aircast boot, surgery, amputation.
(Charcot neuroarthropathy: MRI of foot).

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