A PRACTICAL GUIDE TO

INSULIN THERAPY
Dr AO Williams
Consultant Physician/ Endocrinologist
EDM Unit
LASUTH Ikeja
OUTLINE
• INTRODUCTION
• HISTORY OF INSULIN
• NORMAL PHYSIOLOGY OF INSULIN SECRETION
• CLASSIFICATION OF INSULIN
• PHARMACOKINETIC PROPERTIES OF INSULIN
• INDICATIONS FOR INSULIN THERAPY
• INSULIN DOSING, TITRATION AND SBGM
• CASE SCENARIOS
• SUMMARY
INTRODUCTION
• Insulin is a peptide hormone that is synthesised by the β pancreatic
islet cells.

• It regulates CHO, protein and fat metabolism and a state of

normoglycaemia .

• It is composed of 2 chains α- chain (21 aa) and a β- chain (30aa) linked

together by a disulphide bond.
HISTORICAL BACKGROUND
• 1921- Insulin was first extracted from pancreas of pigs by Banting and
Best
• 1922- first administered to a 14yr old boy at Toronto General Hospital
• 1936- Hans Christian Hargedon discovered that adding protamine to
insulin molecule increased the half life. Zinc was further added to
increase the stability (NPH)
• 1980- Recombinant DNA technology was used to synthesise human
insulin
• 1996- Analogue insulin lispro was first marketed by Lilly
NORMAL INSULIN SECRETION
• The human pancreas secretes about 30 units of insulin per day into
the portal circulation of normal adults in distinct pulses with a period
of approximately 5 minutes.

• The basal concentration of insulin in the peripheral blood in the

fasting state averages 10µU/mL (0.4 ng/mL, or 61 pmol/L) and seldom
rises above 100µU/mL (6 10 pmol/L) post prandially.
NORMAL INSULIN SECRETION
• After ingestion of food, peripheral insulin concentration increases
within 8 to 10 minutes and peaks by 30 to 45 minutes, and then
rapidly declines to basal levels by 90 to 1 20 minutes postprandially.
• Stimulated insulin secretion occurs in response to an ingested meal
with plasma glucose >100mg/dl being the major stimulant.
• Insulin secretion is biphasic : the first phase is a brief burst of insulin
release following a sudden rise in plasma glucose levels.
• The 2nd phase is a slow sustained release on account of a persistently
elevated plasma glucose level.
INSULIN ACTION
Insulin facilitates glucose transport into the liver, skeletal
muscles and adipocytes ,by modulation of GLUT4 glucose
transporters.
- Stimulates storage of glucose as glycogen (glycogenesis)
- Stimulates uptake of fatty acids and triglyceride synthesis
in adipose tissues and muscles.
- Inhibits lipolysis resulting in lowering of plasma fatty acid.
- Stimulates amino acid uptake and protein synthesis in the
liver, muscles adipose tissues.
- Inhibits protein breakdown in muscles
CLASSIFICATION OF INSULIN
• Rapid acting
• Short acting
• Intermediate acting
• Long acting
• Biphasic / Premixed
• Basal /prandial insulin
• Concentrated Insulin (U-200, U-300, U-500)
• Fixed ratio combinations: insulin and another injectable glucose lowering agent ( LIRA +Degludec ),
lixisenatide + glargine
• Non injectable insulin: Technosphere inhaled insulin (Afrezza)
• Oral insulin ( undergoing clinical trials)
INSULIN ONSET PEAK DURATION
Insulin Lispro 0-15min 1 hr 3-5hrs
Insulin aspart 10-20min 1-3hrs 3-5hrs
Insulin glulisine 0-15min 1hr 3-5hrs
Soluble insulin 30-60min 2-3hrs 6-8hrs
isophane 60-90min 4-12hrs 18hrs
Biphasic 30/70 30min 1-8hrs 14-16hrs
Biphasic 25/75 0-15min 1-8hrs 14-16hrs
Biphasic 50/50 0-15min 1-8hrs 14-16hrs
Insulin glargine 1-2hrs nil 24hrs
Insulin detemir Dose dependent minimal Dose dependent up to
28hrs

Insulin degludec 30-90min nil 42hrs

INSULIN NOVO LILLY SANOFI BIOSWISS
Rapid acting Novorapid Humalog Apidra
(aspart) (lispro) (glulisine)
Short acting Actrapid Humulin R Insuman Biosulin R
(Soluble) (soluble) (soluble )
Intermrediate Insulatard Humulin N Biosulin N
(isophane) (isophane
Long acting Levemir Lantus (insulin
(detemir) glargine)
Tresiba (insulin
degludec)
Biphasic Mixtard30 Humulin 70/30 Insuman Biosulin 30/ 70
combo
Novomix 30 Humalog 25
Humalog 50
INDICATIONS FOR INSULIN THERAPY
• Hyperglycaemic emergencies : HHS , DKA
• TYPE 1 DM
• In-patient care
• Perioperative care
• Gestational DM/ DM in pregnancy
• DM in pregnancy in Labour
• TYPE 2 DM with HBA1C >9%
• Type 2 DM on maximal doses of 2 OAD agents with HBA1C > 7.5%
• Type 2 DM who cannot tolerate OAD agents.
INSULIN ADMINISTRATION
• As a continuous intravenous infusion (infusion pump or GKI)
• Deep I.M.
• S.C.
• Continuous subcutaneous Infusion ( insulin pump)
• Various regimens : Basal /bolus
Basal plus
Premixed regimen
Basal insulin with OAD

Best insulin regimen is the one that mimics the body's physiological insulin synthesis and
release pattern
OUTPATIENT ADMINISTRATION OF
INSULIN
• Calculate the total daily dose required
• Determine the insulin regimen to be used
• Determine glycaemic targets
• Patient education: Insulin administration
Hypoglycaemia
Glycaemic targets
SBGM
CALCULATING INSULIN DOSE
T1 DM : O.5-1U/Kg
• Basal bolus regimen:
50% of total dose given as basal insulin
50% given in divided doses of prandial insulin
• e.g. A T1 DM px who weighs 60kg on a dose of 0.5U/kg with a total
daily dose of 30U will have 15U of basal insulin and 5U of prandial
insulin tds with meals.
CALCULATING INSULIN DOSE
T1 DM
• Conventional regimen:
Premixed Human insulin: 2/3rd of total dose with breakfast
and 1/3rd with dinner.
Premixed analogue insulin: Equal divided doses with breakfast
and dinner
• e.g. A T1 DM px who weighs 60kg on a dose of 0.5U/kg with a total
daily dose of 30U will have 20U am and 10U pm of Mixtard 30 or 15U
b.d. of Novomix 30.
CALCULATING INSULIN DOSE
• T2 DM:
• Initiate insulin therapy with basal insulin 0.1-0.2 U/kg (10U) up to a max dose of 0.5U/Kg.
• At maximum dose of basal insulin or when there is post prandial Hyperglycaemia, further
intensification of insulin therapy:
Premixed insulin
Basal plus
Basal- bolus
• Premixed human insulin can be initiated at a dose of 0.3-0.5 U/kg and 2 divided doses
2/3rd before breakfast and 1/3rd before dinner.
• Premixed analogues initiated as a single dose 10U (0.1-0.2U/kg) and up-titrated to
achieve normal FPG.
IN PATIENT CARE OF DM PATIENT
Insulin is the preferred treatment modality in the
hospital setting because:
• It is the most potent agent to lower blood glucose,
• It is rapidly effective,
• It is easily titrated
• It has no absolute contraindications
• Minimal to no drug-drug interactions
 CALCULATING TOTAL DAILY INSULIN
DOSE (IN Px CARE)
• Determine the mode of administration (IV with infusion pump, SC, GKI)
SC administration:
• Basal bolus regimen is recommended for inpatient care.
• Use patients’ body weight, habitus and diabetes status : 0.3-0.6U/kg( T2 DM), 0.5-1U/kg (T1
DM).
• Give previous total daily dose of insulin prior to hospitalization
• Following Hyperglycaemic emergency give total dose of insulin that brought patient to
<250mg/dL
• Ratio of basal to bolus insulin is 50/50 for T1M and at least 1/3 rd of total insulin being basal
in T2DM.
• In patients with poor appetite basal insulin can be increased to 40-50% of total insulin in
T2DM patients.
 CALCULATING TOTAL DAILY INSULIN
DOSE (IN Px CARE)
• Give about 80-110% of total daily IV insulin depending on level of glycaemic
control.
• Determination of intravenous infusion rate is as follows:
Units of insulin per hour = (blood glucose – 60) × 0.02.
When the blood glucose level has not dropped by at least 15%
increase the multiplier by 0.01.
• If RBS 4-7.6 mmol/L give 2U/hr , if 7.7-10mmol/L give 3U/hr If
>10mmol/L give 4U/hr.
• Increase or decrease infusion dose by 1U per hour to maintain RBS at target.
MONITORING BLOOD GLUCOSE
In px:
IV infusion: hourly-4hrly
SC: 8point RBS – 4 point
Out px: SBGM:
 before insulin administration
 FPG and at bedtime( for px on basal insulin)
 PPG check a few times a week
 if having symptoms of hypoglycaemia
 following an insulin dose titration
 Potential Indications for IV Insulin Therapy20.

Janet L. Kelly Diabetes Spectr 2014;27:218-223

©2014 by American Diabetes Association

GLYCEMIC TARGETS IN HOSPITALIZED PATIENTS

•  Insulin therapy should be initiated for treatment of persistent

hyperglycemia starting at a threshold ≥180 mg/dL (10.0 mmol/L).
• Once insulin therapy is started, a target glucose range of 140–180
mg/dL (7.8–10.0 mmol/L) is recommended for the majority of
critically ill patients and noncritically ill patients. A
• More stringent goals, such as 110–140 mg/dL (6.1–7.8 mmol/L), may
be appropriate for selected patients, if this can be achieved without
significant hypoglycemia. C
DISCHARGING PATIENTS ON INSULIN
• ADA recommends that all patients with RBS ≥ 140mg/dL should have
their HBA1C checked.
• This helps to differentiate reactionary Hyperglycaemia from undiagnosed
DM and also to guide outpatient pharmacotherapy post discharge.
• Insulin regimen options for discharge: basal/ bolus
premixed insulin
basal insulin
• When converting basal/bolus regimen to premixed insulin reduce total
insulin dose by 20-30%
INSULIN THERAPY IN PREGNANCY
• 1st trimester : 0.7-0.8 U/kg/day
• 2nd trimester : 0.8-1U/kg/day
• 3rd trimester 0.9-1.2U/kg/day
• Target :HBA1C <6%
FBS <95mg/dL
1HPP<140mg/dL
2HPP<120mg/dL
Nocturnal RBS>60mg/dL
INSULIN THERAPY IN PREGNANCY
• Intensive regimen: Multiple daily injections (basal/bolus)
Continuous Subcutaneous insulin infusion
• Conventional therapy :Total dose is divided to 2/3rd in the morning
and 1/3rd in the evening.
• 2/3rd of morning dose is prandial insulin , 1/3rd is intermediate , half of
evening dose is prandial and remaining half is intermediate.
• Increase insulin dose by 10-20% within 3-7 days if patient is not at
target.
INSULIN THERAPY IN LABOUR
• Ideal to give insulin as an infusion prepared by mixing 50 units of soluble insulin with
49.5mls of 0.9% saline.
• IV 10% dextrose with 10mmol KCl to run at 100mL/hr. (2U/hr)
• Rate of insulin is based on blood glucose levels
<4mmol/l(70mg/dl) - withhold insulin infusion , monitor RBS
4.1-7mmol/l (70- 126mg/dl) - 1-2U/hr
7.1-9mmol/l (126- 162mg/dl) - 2-3U/hr
9.1-11mmol/l (163- 199mg/dl)- 4U/hr
>11mmol/l(200mg/dl) - 6U/hr
Target RBS 4-7mmol/l
Monitor RBS hrly in the first stage of labour and half hrly in the second stage
Case 1 :
• A 58-year-old gentleman working as a lawyer, known to have
T2DM for 10 years, systemic hypertension, and dyslipidemia, is
on tablet metformin 1 g twice daily, tablet glimepiride 4 mg twice
daily, tablet sitagliptin 50 mg once daily, tablet telmisartan 40 mg
once daily, and tablet atorvastatin 10 mg bedtime. His biochemical
evaluation shows fasting plasma glucose of 210 mg/dl,
postprandial plasma glucose of 280 mg/dl, and HbA1c of 8.5%.

• Question: What would you advise?

Case1: answer
• This individual has uncontrolled T2DM despite being on maximum dose of oral
glucose-lowering agents (OGLAs).
• Augmentation therapy with basal insulin analog such as glargine or detemir can
be advised at bedtime with an initial dose of 10 units or 0.2 U/kg in addition to the
current OGLAs.
• He should also be educated on self-monitoring of blood glucose (SMBG) and
titration of insulin dose to target the fasting glucose of 80–120 mg/dl and
postprandial glucose of 120–140 mg/dl.
• If on subsequent follow-up, the postprandial sugars show rising trend or if
HbA1c >7%, he can be started with premixed insulin at an initiation dose of 0.3
unit/kg/day with the total dose split into 2/3rd before breakfast and 1/3rd before
dinner and subsequently titrated based on SMBG.
Case 2:
• A 16-year-old boy working as a mechanic’s apprentice presents
with a history of polyuria, polydipsia, and weight loss of 6 kg
over 3 months. His biochemical evaluation shows fasting
plasma glucose –280 mg/dl, postprandial plasma glucose –
380 mg/dl, HbA1c – 10.5%, and glutamic acid decarboxylase
antibody positive.

• Question: How would you manage?

Case 2: answer
• This young man has type 1 diabetes mellitus and thus requires replacement
insulin therapy in the form of basal bolus regimen using short-acting human
insulin or insulin analogs as bolus insulin for prandial coverage and long-acting
insulin analogs or neutral protamine Hagedorn (NPH) for basal coverage.
• Based on the economic status of this patient, he can be advised regular insulin
with each meal and bedtime NPH.
• He can be started on 0.5 U/kg/day of total insulin dose which can be split into
40% dose as NPH bedtime and 60% regular insulin for prandial coverage (20%
before breakfast, lunch, and dinner). He must be educated on dietary plan,
physical activity, SMBG, and hypoglycemic symptoms.
• The insulin has to be titrated based on SMBG reading every 2–3 days.
Case 3
• A 34-year-old woman presents at 28 weeks' gestation with 75 g
oral glucose tolerance test of fasting 118 mg/dl, 1 h
glucose - 328 mg/dl, and 2 h glucose - 242 mg/dl. Urine ketones
were negative. Clinically, she is obese with signs of insulin
resistance in the form of acanthosis nigricans.

• Question: What would be the management plan?

Case 3: Answer
• This woman has overt diabetes in pregnancy and needs strict
glycemic control to prevent maternal and fetal complications..
• Insulin therapy in the form of basal bolus would be advised. She
can be started with a total insulin dose of 0.8-0.9 units per Kg
and titrated to achieve FPG (target: 60–90 mg/dl) and 1 hr
postprandial glucose (target: 100–140 mg/dl).
• She could also be placed on tablet metformin 500 mg twice
daily which can be increased to a maximum of 1 g twice daily
with insulin therapy.
Case 4
• A 38-year-old woman diagnosed to have type 2 diabetes for
6 years, well controlled on tablet metformin 1 mg twice daily and
tablet gliclazide 40 mg twice daily, is admitted with autoimmune
hemolytic anemia. She is now started on tablet prednisolone
60 mg/day. Blood glucose monitoring shows fasting glucose of
360 mg/dl and postprandial glucose of 420 mg/dl, with negative
urine ketones.

• Question: What would you advise?

Case 4: answer
• This woman has corticosteroid-induced worsening of glycemic
status.
• In addition to the current oral anti-diabetic agents, this patient
needs insulin therapy either in the form of basal bolus insulin
regimen which would be ideal or twice daily premixed insulin at
an initial dose of 0.3–0.5 U/kg/day with subsequent dose
titration based on SMBG.
• This patient must also be educated on reduction of insulin dose
based on SMBG during the period of steroid withdrawal.
Case 5
• A 14-year-old male student with type 1 diabetes of 5 years' duration on three
times regular insulin and NPH at bedtime, fairly compliant with treatment, has
come for review. His SMBG record shows persistently high fasting and
postprandial sugars despite increasing the insulin dose. He complains of
hypoglycemic symptoms at midnight 2 weeks earlier which was treated
symptomatically, however no reduction in insulin dose was made the next day.
For the past 2 weeks, he is symptom free. He is also taking regular insulin just
before his meals as he finds it difficult to wait for 30 min in his busy school
schedule.

• Question: How would you manage this patient?

Case 5: answer
• This patient probably has the Somogyi effect due to midnight hypoglycemia
and has also developed hypoglycemic unawareness due to recurrent
hypoglycemic events.
• It would be advisable to switch the patient from NPH, which can lead to
midnight hypoglycemia during its peak effect, to a long-acting insulin analog
with peakless profile such as glargine or detemir.
• Rapid-acting insulin analogs can be advised as premeal bolus insulin
instead of regular insulin as they can be taken 15 min prior or immediately
after meals.
• Dietary counseling and bedtime snack is also an important aspect of
management to prevent hypoglycemia in this patient.
Case 6
• A 55-year-old woman with T2DM of 5years duration was admitted
at the ER on account of polyuria, polydipsia and altered sensorium
and RBG was unrecordably high. She is markedly dehydrated but
still has a urinary output of about 70mL per hour . She weighs
80kg, PR is 104b/min, BP is 100/78mmHg She was currently on
tablet Metformin 2g daily, glimepiride 3 mg/day. Her HbA1c was
8.6%.

• Question: How will you manage this patient?

• Discuss her insulin regimen from period of admission to discharge
Case 6: answer
• Hydrate patient with IVF N/saline (15-20mL/kg/hr maintain @ 4-14mL/kg/hr).
• Re evaluate RBS and hydration status after 1hr
• Commence insulin infusion @ 0.1U/kg/hr to achieve RBS 250-300mg/dL
• Then calculate total dose that brought patient to RBS of 250mg/dL and give as
SC using basal bolus regimen with 30-40% of total dose as basal insulin and
60-70% as 3 divided doses of prandial insulin.
• Titrate dose of insulin to achieve FPG and premeal target of 90-130 and
prandial target <180mg/dL.
• Discharge on basal bolus or premixed regimen
• Give 2/3rd of total insulin dose as premixed insulin.
•THANK YOU