Insulin initiation and intensification in patients with T2DM for the primary care physician

Figures & data

Table 1 Proposed stages of β-cell decompensation and dysregulation¹⁰

Stage	Ambient blood glucose value	Physiologic changes within islet/β-cell	Histologic changes noted within islet/β-cell
Stage 1	85–130 mg/dL	Lowered set-point for glucose-stimulated insulin secretion due to glucokinase activation	Normal gene expression profile β-cell hypertrophy β-cell hyperplasia
Stage 2	89–130 mg/dL	Loss of first-phase insulin response Near-normal insulin stores	Decreased expression of glucokinase, glucose transporter proteins, and transcription factors
Stage 3	130–285 mg/dL	Loss of second-phase insulin secretion Increased ratio of proinsulin: insulin, suggestive of β-cell injury Patient is maximally insulin resistant as 80% of the β-cell function is lost	Reduced insulin stores within β-cell Increased expression of genes which predispose to loss of β-cell mass and function In obese patients, up to 40% of the β-cell mass is lost
Stage 4	285–350 mg/dL	β-cell apoptosis and death	Amyloid and lipid deposits form within islets Islets become fibrosed
Stage 5	>350 mg/dL	Marked β-cell destruction Loss of signaling between the α- and β-cell can increase risk of hypoglycemia	Fibrosis

Table 2 Proactive questions related to hypoglycemia

When did the event(s) occur? (daytime vs overnight) Under what circumstances did they occur? (missed meal, following exercise, excess medication) What were the symptoms? What was the blood glucose reading? How did patient treat the hypoglycemia? Did the patient require assistance from another person in order to reverse the hypoglycemia? Did the hypoglycemic event re-occur later within a 24-hour period? What was done? (eg, carbohydrates ingested, follow-up blood glucose monitoring) How soon did hypoglycemia resolve? (Blood glucose levels rose to >70 mg/dL) How fearful is the patient or the family of hypoglycemia? Do they test before driving? Do patients “stack insulin” (re-bolus rapid insulin analog within 3 hours of a similar injection)? At what glycemic level does the patient perceive hypoglycemia? (If <50 mg/dL, patient may have hypoglycemia-associated autonomic failure).

Table 3 Strategies for initiating and titrating insulin for treatment-naïve patients with T2DM

Suggest that insulin will help patients achieve glycemic targets and minimize the risk of long-term complications Allow patients to actively participate in their insulin dose titration Always praise patients on insulin at their visits for their efforts at achieving their glycemic targets ○ Remember, patients who are using insulin do not have normally functioning pancreases ○ They are performing their own insulin dose calculations, perhaps multiple times each day ○ Insulin prescribers should do everything possible to help patients become successful users of insulin Individualize therapy to meet the needs of each patient ○ Determine which treatment algorithm might work best for every patient Emphasize the importance of lifestyle intervention ○ This should minimize weight gain and reduce PPG excursions Consider group office visits to have patients meet with a certified diabetes educator diabetes educator ○ Often, 8–20 patients can be seen at group visits; they are time-efficient and reimbursable by third-party payers Provide each patient with an individualized, written insulin protocol to which they can refer Prescribe insulin pen devices whenever possible ○ Dose titration of insulin is much more accurate with pens than with vials and syringes Teach patients how to identify and appropriately manage hypoglycemic events When initiating basal insulin, use 0.4 U/kg/day as the starting dose ○ Continue metformin if possible If patient requires > 60 U of basal insulin per day, and his or her A1C level is >7%, add a rapid-acting insulin analog at the largest meal of the day ○ The dose for rapid-acting insulin is 0.1 U/kg/meal If A1C level is not reduced to target after 3 months of basal plus bolus insulin, add a second injection at the next largest meal of the day ○ Repeat the A1C test at 3 months and if still above target, add a third mealtime injection Patients on basal-bolus insulin therapy should consider modified paired glucose testing in order to fine-tune their treatment regimens

Abbreviations: A1C, glycosylated hemoglobin; PPG, postprandial glucose; T2DM, type 2 diabetes mellitus.

Table 4 SimpleSTEP™ or ExtraSTEP algorithm⁴⁶

Efficacy	Period 1	Period 2	Period 3	Period 1	Period 2	Period 3
SimpleSTEP ExtraSTEP
A1C (%)	8.2	7.7	7.6	8.5	7.9	7.7
FPG (mmol/L)	8.2	7.6	7.6	8.0	7.6	7.4
Hypoglycemia (episodes/yr)
Requiring assistance	0	0	0.14	0.03	0	0
No assistance PG < 3.1 mmol/L	3.5	6.1	8.8	3.3	5.5	9.3
Weight change at end of trial (kg)		2.7			2.0

Abbreviations: A1C, glycosylated hemoglobin; FPG, fasting plasma glucose; PG, plasma glucose.

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