1) Insulin replacement aims to mimic the body's natural pulsatile insulin secretion, with about half from basal insulin and half from prandial excursions. Different insulin preparations have varying onset, peak times, and durations of action that inform their use. 2) Monitoring of glycated hemoglobin (HbA1c), fasting blood glucose, and post-prandial blood glucose helps assess diabetes management. Initial insulin treatment focuses on basal insulin, with adjustments to prandial insulin as needed based on monitoring. 3) Insulin regimens must be tailored to the individual, starting at low doses and gradually titrating based on blood glucose levels. Multiple insulin types and combinations can be used

1. MANAGEMENT OF
DIABETES MELLITUS-
INSULIN TREATMENT
PRESENTED BY
DR. ANKUR SABHERWAL
DEPARTMENT OF MEDICINE
PGIMER SATELLITE CENTRE SANGRUR

2. PHYSIOLOGIC INSULIN REPLACEMENT
 Insulin release is pulsatile
 About half of 24 hr insulin is made of basal insulin secretion
 Other half comes from prandial (mealtime) excurtions

3. PHARMACOKINETICS OF COMMONLY USED
INSULIN PREPERATIONS – PRANDIAL INSULIN
INSULIN TYPE APPROXIMATE ONSET
OF ACTION
EFFECTIVE PEAK APPROXIMATE
DURATION OF
LISPRO, ASPART,
GLULISINE
15-30 min 1-3 hrs 4-6 hrs
REGULAR 30 min 1.5- 3 hrs 8 hrs

4. PHARMACOKINETICS OF COMMONLY USED
INSULIN PREPERATIONS – BASAL INSULIN
INSULIN TYPE HALF LIFE EFFECTIVE PEAK APPROXIMATE
DURATION OF
NEUTRAL PROTAMINE
HAGEDORN (NPH)
4.4 hrs 4-6 hrs 12 hrs
U-100
(INSULIN GLARGINE)
12 hrs No pronounced peak 20 to >24 hrs
U-300
(INSULIN GLARGINE)
19 hrs No pronounced peak 20 to > 24 hrs
INSULIN DETEMIR 5-7 hrs 3-9 hrs 6-24 hrs
INSULIN DEGLUDEC
(U-100, U-200)
25 hrs No pronounced peak > 24 hrs

5. MONITORING GLYCEMIA
 Glycated hemoglobin (HbA1c):
- For most patients an HbA1c value of 7.0% is a reasonable therapeutic goal
- For old patients and those with comorbidities or those with limited life expectancy, the HbA1c goal
can be raised slightly
 Fasting blood glucose (FBG) and postprandial blood glucose (PPBG)
- Target for FBS is 80 – 130 mg/dl
- Target for PPBS is less than 180 mg/dl usually measured after 90 – 120 minutes after meal
 Continuous glucose monitoring (CGM)
- CGM devices may be used to monitor sugar continuously throughout 24 hrs without multiple pricks

6. INDICATIONS FOR INSULIN
 Severe hyperglycemia on presentation
- Symptomatic patients (weight loss, polydipsia, polyuria)
- Severe hyperglycemia with ketonuria
- Insulin or GLP-1 receptor agonist is an option, along with metformin for patients for patients who present with severe
hypoglycemia (FBG > 250 mg/dl, RBS consistently > 300 mg/dl and HbA1c > 9 %) but who do not have ketonuria or
spontaneous weight loss in whom type 1 diabetes mellitus is unlikely
 Difficulty distinguishing type of diabetes
 Pancreatic insufficiency (cystic fibrosis, chronic pancreatitis, pancreatectomy
 Persistent hyperglycemia on oral agents
- For patients with HbA1c >9% or persistent symptoms of hyperglycemia despite metformin titration , Insulin or GLP-1
receptor agonist is the preferred second line treatment
- In insulin deficient , catabolic diabetes, insulin is preferable

7. DESIGNING AN INSULIN REGIMEN
 Basal insulin to be started first as
- Initial treatment
- In addition to oral medication
- In substitute of oral medication
 It improves FBG and nocturnal blood glucose levels

8. CHOICE OF BASAL INSULIN
 Single daily dose of insulin NPH, Detemir, Glargine or Degludec
 Administer either in morning or bedtime
 Bedtime NPH or detemir to be taken at 10 PM and test FBS at 7 or 8 AM
 Initial dose at 0.2 units per kg ( minimum 10 U and upto 15-20 units)
 Higher dose at 0.3 units per kg to be if FBS levels are extremely high (> 250
mg/dl) , HbA1c is > 8% or patient is known to be extremely insulin resistant
 Measure FBS daily and HbA1c every 3 months

9. COMBINATION THERAPY
 Prevents weight gain
 Total insulin requirement is less
 GLP-1 receptor agonists and SGLT-2 inhibitors can be continued when insulin is
added especially if they are used for cardiac or renal benefit
 DPP-4 inhibitors add add cost and complexity and are relatively weak, so they
may be stopped when insulin is initiated
 Sulphonylureas, meglitinides and pioglitazone are typically tapered and
discontinued because of there decreased efficacy and side effects

10. INSULIN MONOTHERAPY
 Causes slightly more weight gain and increased number of episodes of
hypoglycemia, most of which are not severe
 After patient is on sufficient dose of basal insulin or when insulin is first added,
oral medication may be stopped

11. TITRATING DOSE
 If mean FBS is above target (typically > 130 mg/dl), increase dose of basal insulin
by 2-4 units, approximately every 3 days
 If mean FBS is in target range (90-130 mg/dl) but HbA1c is elevated, start prandial
insulin with a single injection prior to largest meal of the day

12. PRELUNCH GLUCOSE ELEVATED
 Add prandial glucose before breakfast
 Add a GLP-1 receptor agonist
 Add a second dose of NPH or detemir at breakfast
 Breakfast dietary changes
 Taking two doses of detemir insulin achieves more stable 24 hr glucose control
 Divide 80% of current bedtime dose of detemir insulin in two parts of 50% each , give
one dose in morning, one at bedtime
 For NPH insulin, divide 80% of the current bedtime dose in two parts of 70% and 30%,
give 70% dose in morning and 30% dose at bedtime
 For patients who are far from glycemic goals, the full daily dose of detemir can be
administered in equally divided doses

13. PREDINNER OR BEDTIME GLUCOSE
ELEVATED
 Add prandial dose of regular or short acting insulin before dinner
 Eat a smaller lunch and cover dinner with prandial insulin
 Employ reverse strategy (smaller dinner and cover lunch with prandial insulin) if
lunch is the biggest meal
 Adding GLP-1 receptor agonist is another option
 Add second dose of NPH or detemir insulin at breakfast if both prelunch and
predinner glucose levels are excessive

14. COMBINING PRANDIAL AND BASAL
INSULIN
 Keep basal and premeal insulin injections separate and adjust them independently
 Premeal and NPH insulin can be drawn into the same syringe prior to injection
 Glargine, degludec and detemir cannot be mixed with rapid acting insulin

15. CHOICE OF PRANDIAL INSULIN
 Based on patients preference, availability and cost
 Rapid acting insulins have a slight glycemic advantage over normal insulin,
notably in patients with T1DM
 Rapid acting insulins can be given 10-15 min prior to meals whereas short acting
insulins can be given 30-45 minutes prior
 Adherence to rapid acting insulins is better
 In T2DM , glycemic advantage of rapid acting insulin over regular insulin is
negligible

16. PREMEAL INSULIN DOSING
 Depends on many variables such as activity levels, meals carbohydrate content, and
current and target blood glucose levels
 Usual starting dose is 4-6 units or 10% of the baseline insulin dose
 Till desired postprandial glucose level is reached, dose can be raised every 3 days
 As a rule of thumb, the dose is increased according to prior dose as follows
- < 10 units – increase by 1 unit
- 10-20 units – increase by 2 units
- > 20 units – increase by 5 units (or more depending on meal size, content and insulin
resistance)

17. PREMIXED INSULIN
 Give dose before meals
 Calculate total daily dose based on weight (0.2 units/kg body weight) or based on
prior insulin dose
 Administer two thirds of daily dose before breakfast and one third dose before
dinner ( or reverse if dinner is biggest meal)
 Premixed insulin should be dosed relative to meal intake and may need to be
reduced for smaller meals
 Dose is adjusted based on glucose monitoring
 If prelunch and predinner hyperglycemia is occurring, morning dose can be
increased by 2-3 units every 2-3 days

18. CONVERSION BETWEEN BASAL INSULIN
PRODUCTS
 Change from twice daily (NPH or detemir) to once daily (glargine or degludec) insulin
- Decrease total daily dose of insulin by 10-20% and retitrate based on blood glucose
levels
- If patient is severely hyperglycemic without any signs of hypoglycemia, comparable
daily dose of once daily long acting insulin can be given
 Conversion between one daily insulins
- Decrease the dose by 10-20% if patient is switching from once daily detemir to once
daily glargine (U-100 or U-300) or degludec
- Give comparable dose if patient has very high blood sugar

19. INSULIN RESISTANCE
 In patients with significant insulin resistance ( those requiring >200 total units of
insulin per day), concentrated insulin formulations (U-300 insulin) can be used
 Smaller volume of injected insulin improves absorption kinetics
 U- 300 glargine insulin has less of a peak and longer duration of action
 It is more similar to degludec
 Insulin sensitizers like Metformin or Glitazones may be used
 Concentrated rapid acting insulin analogues (U-200 lispro and U-200 lispro –aabc)
contain 200 units /ml instead of 100 units/ml in U-100 preparation
 They are available in prefilled pens and useful for patients requiring high dose of
prandial insulin
 Dose window shows number of units of insulin to be delivered

20. COMPLICATIONS
 Hypoglycemia- seen more in T1DM than in T2DM
 Lipodystrophy on injection sites
 Hypersensitivity reactions
 Weight gain

21. NOCTURNAL HYPOGLYCEMIA
 Decrease dose of bedtime insulin by 4 units or 10% whichever is greater
 If there is no clear hypoglycemia precipitant (e.g. skipped meal or increased
physical activity and increased alcohol intake), greater dose reduction 20-30%
with retitration is needed
 Changing to detemir, degludec or glargine insulin at 80-90% of present daily dose
is an alternative in patient taking bedtime NPH

22. DAYTIME HYPOGLYCEMIA
 Reduce dose of prandial insulin
- < 10 units- decrease by 2 units
- 11-20 units- decrease by 4 units
- > 20 units- decrease by -0 units or 50%
 If patient is not taking prandial insulin, decrease basal insulin dose by 4 units or
10% , whichever is greater
 Switch to long acting nonpeaking insulin

23. SEVERE HYPOGLYCEMIA
 A hypoglycemic event that that necessitates the assistance of another person to
actively administer carbohydrate is severe hypoglycemia
 If hypoglycemia is severe or serious , significantly lower dose (by 20-50%) and
repeat titration or stop using prandial insulin

24. THANK YOU