Published online Jul 15, 2025. doi: 10.4239/wjd.v16.i7.106470
Revised: April 20, 2025
Accepted: June 9, 2025
Published online: July 15, 2025
Processing time: 138 Days and 18.6 Hours
Studies have shown that patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion (CSII) require a lower dose of insulin than those treated with multiple daily injections (MDIs). However, it is unclear whether this is also the case for patients with type 2 diabetes mellitus (T2DM).
To compare insulin dosage requirements between CSII and MDI in T2DM, iden
A total of 954 patients with T2DM were divided into two groups: CSII and MDI groups. The total daily insulin dose (TDD), TDD per kilogram per day (TDD/kg), and ratio of total basal insulin dose to TDD (%TBa) required to achieve the target blood glucose levels were compared between the two groups. In addition, factors affecting insulin dosage were analyzed in both groups of patients.
Compared to the CSII group, the MDI group required a higher TDD [median (interquartile)]: 30.00 (24.00, 38.00) U/day vs 26.40 (21.60, 32.40) U/day; P < 0.01, TDD/kg and %TBa. In the MDI group and CSII groups, an increase in TDD was independently associated with an increase in body mass index (BMI), waist circumference (WC), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c).
Patients with T2DM receiving CSII treatment require a lower dose of insulin to achieve good glycemic control. BMI, WC, FPG, and HbA1c are the main factors affecting insulin dosage.
Core Tip: This study demonstrates that patients with type 2 diabetes mellitus (T2DM) on continuous subcutaneous insulin infusion require a lower dose of insulin than those receiving multiple daily injections, while achieving good glycemic control. Fasting plasma glucose, glycated hemoglobin, body mass index, and waist circumference correlated with increased insulin requirements across both therapies. Our data also suggest that the ratio of total basal insulin dose to total daily dose of approximately 40% (lower than the 50% recommended percentage) may optimize glycemic outcomes. These findings highlight the need for careful selection of insulin therapy and revision of basal insulin recommendations in T2DM management.
- Citation: Sun RM, Dai DX, Xu F, Ling YL, Xie ZJ. Factors influencing insulin requirements in using continuous subcutaneous insulin infusion or multiple daily injections in type 2 diabetes. World J Diabetes 2025; 16(7): 106470
- URL: https://www.wjgnet.com/1948-9358/full/v16/i7/106470.htm
- DOI: https://dx.doi.org/10.4239/wjd.v16.i7.106470
The pathophysiology of type 2 diabetes mellitus (T2DM) mainly involves insulin resistance and progressive β-cell failure, which leads to increased blood glucose levels (hyperglycemia)[1-3]. Treatment for T2DM includes antidiabetic medications and insulin therapy[4,5]. Patients with T2DM with β-cell failure usually require insulin therapy[6-8]. Continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDIs) are two major insulin therapies for controlling hyperglycemia in these patients. However, excessive insulin therapies may cause problems such as hypoglycemia, weight gain, and iatrogenic hyperinsulinemia[9]. Therefore, attention should be paid to the dosage of insulin used.
The establishment of insulin regimens for CSII and MDI therapies is primarily guided by physicians’ empirical judgment. To date, there have been few clear guidelines or recommendations on the appropriate insulin dose during CSII and MDI treatment for T2DM[10]. Yang et al[11] studied insulin doses and related factors in the CSII treatment of patients with T2DM[12]. However, these studies did not cover the dose setting and related factors in MDI treatment. Previous studies have shown that patients with type 1 diabetes mellitus treated with CSII require less insulin than those treated with MDIs[13-15]. However, it is unclear whether patients with T2DM on CSII also require less insulin than patients on MDI.
Therefore, the present study determined the difference in insulin dosages between CSII and MDI therapies and evaluated the related factors in patients with T2DM. It also systematically analyzed the insulin dose characteristics of MDI and CSII in 954 hospitalized patients with T2DM, aiming to optimize the insulin dosage regimen and provide clinical references for guiding the application of CSII and MDI in patients with T2DM.
This study analyzed the electronic medical records of 954 patients with T2DM hospitalized at The Second Xiangya Hospital of Central South University (Changsha, Hunan Province, China) between 2014 and 2022. Participants were stratified into two groups based on insulin administration modality: CSII or MDI. Ethical clearance for this study was formally granted by the institutional review panel, ensuring compliance with the Declaration of Helsinki.
Admission was mandated for uncontrolled hyperglycemia [glycated hemoglobin (HbA1c) > 9.0% or fasting plasma glucose (FPG) > 11.1 mmol/L] requiring rapid titration, critical limb ischemia necessitating revascularization, perioperative glycemic optimization, or exacerbation of chronic complications (e.g., nephropathy progression, non-healing diabetic foot ulcers). Hemodynamic instability, failure of outpatient management, or multidisciplinary care requirements further justified hospitalization.
Insulin therapy was initiated in patients with T2DM under clinical scenarios of persistent hyperglycemia (HbA1c > 7.0%) unresponsive to optimized oral antihyperglycemic agents (e.g., metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists) and lifestyle modifications, severe hyperglycemia at diagnosis (HbA1c > 9.0% or FPG > 11.1 mmol/L) with metabolic decompensation (e.g., ketosis, diabetic ketoacidosis), progressive diabetes complications (i.e. microvascular/macrovascular dysfunction, β-cell failure), or acute physiological stressors (i.e. perioperative periods, infections) requiring rapid glycemic control.
The allocation of insulin delivery modalities-CSII vs MDI-followed a patient-centered algorithm. CSII was prioritized for newly diagnosed individuals with severe hyperglycemia as well as for patients with recurrent hypoglycemia or marked glucose fluctuations. By contrast, MDI was recommended for patients with established cardiovascular or renal comorbidities, or individuals with limited access to CSII technology or challenges in adhering to self-management protocols. Decision making incorporated HbA1c levels, hypoglycemia risk, socioeconomic factors, and patient adherence, with multidisciplinary consensus for complex cases.
Eligible participants were adults diagnosed with T2DM requiring short-term insulin therapy during hospitalization at The Second Xiangya Hospital (2014-2022), who achieved glucose target level prior to discharge and had complete clinical and laboratory records. Patients with acute diabetic complications including diabetic ketoacidosis and hypertonic hyperglycemia, severe chronic diabetes complications, liver dysfunction, and renal insufficiency, heart failure, pregnancy, acute infections and patients with other diseases or using medications were excluded.
All enrolled patients received standardized insulin therapy under a basal-bolus regimen during hospitalization, comprising basal insulin (0.2-0.3 U/kg/day) and preprandial rapid-acting analogs (1 U/10-15 g carbohydrate), with correctional doses administered for capillary glucose levels exceeding 7.8 mmol/L (140 mg/dL)[16]. Therapy was guided by seven-point daily glucose profiles (preprandial, 2-hour postprandial, and bedtime) monitored using a validated glucometer (Bionime Biotechnology-Ping Tan Co., Ltd., Fuzhou, Fujian Province, China). Hypoglycemic events (≤ 3.9 mmol/L) were managed with 15-20 g fast-acting carbohydrates and subsequent regimen adjustments. Patients exclusively received insulin therapy without concurrent oral antihyperglycemic agents. Glycemic targets aligned with the 2019 Chinese Diabetes Health Care Standards[17]: FPG 4.4-7.0 mmol/L and postprandial glucose 4.4-10.0 mmol/L, with therapy duration continued until target adherence was sustained for more than 3 consecutive days. Total daily insulin dose (TDD), TDD per kilogram (TDD/kg), and the ratio of total basal insulin dose (TBD) to TDD (%TBa) were compared between the CSII and MDI groups. In addition, factors affecting insulin dose were analyzed.
Demographic characteristics of patients including sex, age, and age of onset were collected. Body weight and height measurements were utilized to calculate the body mass index (BMI) via the standard formula (weight in kilograms divided by height in meters squared). Waist circumference (WC) was recorded at the midpoint between the inferior costal margin and iliac crest, whereas hip circumference was assessed at the maximal protrusion of the greater trochanter. Venous blood specimens were collected for biochemical profiling including FPG, HbA1c, fasting and postprandial (2-hour) C-peptide levels, and lipids.
Statistical analyses were performed using SPSS 25.0 (IBM SPSS Statistics, Armonk, NY, United States). All descriptive statistics are shown as the mean ± SD or median (lower quartile, upper quartile). Differences among groups were determined by the Wilcoxon rank-sum test or Fisher’s exact test for non-parametric continuous data. Partial correlation coefficients such as BMI, FPG, and HbA1c were used for subgroup analyses to determine whether there was an association between these factors and insulin dose. Influencing factors of TDD, TDD/kg, and %TBa were evaluated by multiple linear regression analysis. Spearman’s rank correlation analysis was used to analyze the relationship between insulin dose and related factors. P < 0.05 was considered statistically significant.
The baseline characteristics of 561 patients on MDI and 393 patients on CSII are summarized in Table 1. Demographic and metabolic parameters including age, sex distribution, HbA1c level, lipid profiles (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and β-cell function markers (fasting/2 hour-postprandial C-peptide) demonstrated no statistically significant intergroup differences between MDI- and CSII-treated cohorts. BMI and duration of diabetes at baseline were significantly different between patients on CSII and MDI (P < 0.01). BMI in the CSII therapy group was significantly higher than that in the MDI therapy group, whereas the duration of diabetes in the MDI therapy group was significantly longer than that in the CSII therapy group.
| Factors | MDI therapy (n = 561) | CSII therapy (n = 393) |
| Age in years, median (interquartile) | 57.0 (49.0, 65.0) | 56.0 (48.5, 64.0) |
| Sex | ||
| Men | 351 (58.5) | 235 (56.6) |
| Women | 249 (41.5) | 180 (43.4) |
| Duration of diabetes in years, median (interquartile) | 10.0 (5.0, 15.0) | 9.0 (3.0, 13.5)b |
| BMI in kg/m2, median (interquartile) | 23.7 (21.7, 26.0) | 24.9 (23.0, 27.0)b |
| WC in cm | 87.7 ± 10.0 | 90.0 (85.0, 96.0)b |
| FPG in mmol/L, median (interquartile) | 8.6 (6.8, 10.8) | 8.3 (6.4, 10.6) |
| HbA1c as %, median (interquartile) | 9.7 (7.8, 11.3) | 9.5 (7.9, 11.0) |
| Fasting C-peptide in nmol/L, median (interquartile) | 302.0 (180.7, 483.7) | 324.3 (217.6, 468.9) |
| 2 hour-postprandial C-peptide in nmol/L, median (interquartile) | 577.4 (305.0, 1051.3) | 609.9 (389.6, 1003.3) |
| Total cholesterol in mmol/L, median (interquartile) | 4.0 (3.6, 5.1) | 4.1 (3.6, 5.2) |
| LDL cholesterol in mmol/L, median (interquartile) | 3.3 (2.4, 3.4) | 3.4 (2.6, 3.5) |
| HDL cholesterol in mmol/L, median (interquartile) | 1.0 (0.8, 1.4) | 1.0 (0.8, 1.3) |
| Triglycerides in mmol/L, median (interquartile) | 1.7 (1.3, 2.2) | 1.7 (1.4, 2.3) |
Patients who used MDI therapy needed higher TDD, TDD/kg, and %TBa than those on CSII therapy [TDD: 30.00 (24.00, 38.00) U/day for MDI vs 26.40 (21.60, 32.40) U/day for CSII, P < 0.01; TDD/kg: 0.49 (0.38, 0.60) U/kg for MDI vs 0.40 (0.32, 0.49) U/kg for CSII, P < 0.01; %TBa: 43.00% (36.00%, 50.00%) for MDI vs 42.00% (40.00%, 50.00%) for CSII, P < 0.01] after adjustment for disease duration and BMI (Table 2).
| Patients | Therapy | TDD | TDD/kg | TBa% |
| All patients, median (interquartile) | MDI therapy (n = 561) | 30.00 (24.00, 38.00) | 0.49 (0.38, 0.60) | 43.00 (36.00, 50.00) |
| CSII therapy (n = 393) | 26.40 (21.60, 32.40)b | 0.40 (0.32, 0.49)b | 42.00 (40.00, 50.00)b | |
| HbA1c < 8%, median (interquartile) | MDI therapy (n = 153) | 25.00 (21.00, 29.00) | 0.41 (0.33, 0.48) | 44.40 (40.00, 49.00) |
| CSII therapy (n = 103) | 21.60 (16.80, 27.00)a | 0.36 (0.29, 0.42)a | 40.00 (30.00, 50.00)a | |
| HbA1c ≥ 8%, median (interquartile) | MDI therapy (n = 408) | 31.00 (26.00, 39.00) | 0.51 (0.42, 0.62) | 45.30 (36.40, 53.70) |
| CSII therapy (n = 290) | 27.20 (21.70, 33.00)b | 0.43 (0.34, 0.50)b | 44.40 (40.00, 50.00) |
In patients with HbA1c baseline levels below 8% (64 mmol/mol), TDD, TDD/kg, and %TBa in the MDI therapy group were significantly increased compared to those in the CSII group. In patients with HbA1c baseline levels ≥ 8% (64 mmol/mol), TDD and TDD/kg in the MDI group were significantly higher than those in the CSII group. However, there was no significant difference in %TBa between the CSII and MDI therapy groups (Table 2).
TDD and TDD/kg were positively correlated with BMI, WC, baseline FPG, and HbA1c in both the CSII and MDI treatment groups. %TBa was positively correlated with WC and baseline FPG in both groups. %TBa was positively correlated with HbA1c in the MDI group (r = 0.16, P < 0.001). However, %TBa did not correlate with HbA1c in the CSII group (r = 0.07, P = 0.15) (Table 3).
Multiple linear regression models incorporating age, diabetes duration, BMI, HbA1c, WC, and baseline FPG were constructed to identify independent predictors of insulin demand parameters. In patients with MDI treatment, BMI (r = 0.26), WC (β = 0.30), HbA1c (β = 0.24), and baseline FPG (β = 0.18) were independent predictors of TDD (all P < 0.01). BMI (r = 0.19, P < 0.01), HbA1c (β = 0.25, P < 0.01), and baseline FPG (β = 0.18, P < 0.01) were independently correlated with TDD/kg. %TBa was independently correlated with FPG (β = 0.21, P < 0.01) (Table 4).
In the CSII group, TDD was associated with BMI (r = 0.19, P < 0.05), WC (β = 0.20, P < 0.05), HbA1c (β = 0.22, P < 0.01), and baseline FPG (β = 0.28, P < 0.01). HbA1c (β = 0.23, P < 0.01) and baseline FPG (β = 0.29, P < 0.01) were independently correlated with TDD/kg. Interestingly, %TBa was independently correlated with age (β = -0.15, P < 0.05), BMI (r = -0.27, P < 0.05), WC (β = 0.37, P < 0.01), and FPG (β = 0.22, P < 0.01) (Table 5).
This study demonstrated that CSII significantly reduced TDD compared to MDI in T2DM patients with suboptimal baseline glycemic control [HbA1c ≥ 8% (64 mmol/mol)]. Crucially, our HbA1c-stratified analysis revealed that this CSII advantage was specifically pronounced in this poorly controlled subgroup. Furthermore, we identified that TBD constituted approximately 40% of TDD-lower than current recommendations[11,12]-was physiologically appropriate for Chinese T2DM patients irrespective of therapy (CSII or MDI). Finally, we established that FPG, HbA1c, BMI, and WC were independent predictors of TDD across both insulin delivery modalities.
Currently, it is generally believed that CSII is superior to MDI for the treatment of type 1 diabetes mellitus; however, there is still controversy over which of these two treatments is relatively better for T2DM[13-15,18]. Some studies have suggested that CSII is better than MDI treatment for T2DM in terms of glycemic control[19-22]. However, the results from other studies have shown no differences between CSII and MDI therapies for T2DM regarding glycemic control[23-25]. The OpT2mise study, a randomized, prospective, controlled trial, showed that switching from MDI to pump therapy resulted in a 20% reduction of TDD[21]. Similarly, Morera et al[26] observed in a retrospective cohort study that 161 patients with T2DM who had been treated previously with MDIs and received pump treatment experienced TDD decrease by 13%. The results of these studies suggest that, similar to findings in patients with type 1 diabetes mellitus[15], using CSII to treat T2DM can significantly reduce insulin doses.
Glycemic control level significantly influences the choice of insulin treatment; therefore, we divided patients into two groups according to the levels of HbA1c. Our results showed that in patients with T2DM whose HbA1c baseline levels were below 8% (64 mmol/mol) treated with CSII, the TDD, TDD/kg, and %TBa were significantly decreased (P < 0.05). In patients with T2DM with HbA1c less than 8% on CSII treatment, TDD was reduced. Although reducing TDD/kg is beneficial, reducing TBa% may not necessarily be beneficial. It has been shown that TBD is effective for controlling FPG and HbA1c[27]. TBD reduces not only FPG and preprandial blood glucose but also partially reduces postprandial hyperglycemia. The reduction in %TBa in patients receiving CSII treatment means a higher dose of insulin is needed before meals. An increase in insulin dosage before meals can enhance the cumulative effect of the basal dose, leading to additional adjustments in TBD. Therefore, for patients with T2DM with HbA1c less than 8% (64 mmol/mol), the choice of CSII or MDI treatment remains a subject of debate. Patients with HbA1c ≥ 8% (64 mmol/mol) receiving MDI therapy exhibited significantly greater TDD and TDD/kg compared to their CSII-treated counterparts, whereas %TBa showed no intergroup difference. Given that there was no difference in %TBa between the two groups of patients with T2DM, it had no effect on preprandial glucose or additional adjustments on the TBD. As a lower dose of insulin may have helped reduce insulin resistance and hypoglycemia risk, the results indicated that CSII treatment is a better choice than MDIs for patients with T2DM whose baseline HbA1c levels are ≥ 8% (64 mmol/mol). Furthermore, CSII therapy achieved better glycemic control than MDIs in patients with T2DM and poor diabetes control at baseline.
Previous studies have shown that TBD accounts for 40% of TDD in patients with T2DM treated with CSII, which is lower than the recommended percentage[11,12,28]. However, for patients with T2DM who receive MDI treatment, it remains unclear whether TBD of 50% of TDD is more reasonable. The present study showed that in patients with T2DM, TBD for MDI and CSII therapies was about 40% of TDD. This discrepancy may reflect unique pathophysiological and cultural determinants of glucose dysregulation. Chinese dietary patterns characterized by high carbohydrate intake from staple foods like rice and noodles, drive postprandial hyperglycemia dominance. Therefore, for T2DM among Chinese populations, a TBD of 40% of TDD may be more reasonable, regardless of the treatment modality of CSII or MDI, which is lower than the current recommended percentage.
Our results indicated that patients with a higher BMI require higher TDD to reach the target blood glucose level in either the MDI or CSII treatment group, which is consistent with previous studies[11,12,29,30]. The current study also showed that patients with higher levels of HbA1c require higher TDD to achieve the target glucose level. WC is an indicator of central obesity and insulin resistance, and a higher WC may lead to more severe insulin resistance to some extent[31-33]. Our results indicate that patients with a higher WC require higher TDD for both MDI and CSII therapies. Previous studies have shown that in patients on CSII therapy, FPG, HbA1c, BMI, and WC are independently associated with TDD[11,12]. However, it is unclear whether this association is present in patients on MDI. The results from the present study indicate that FPG, HbA1c, BMI, and WC are independently associated with TDD in patients on either MDI or CSII therapy. Despite the strengths of the present study, including a relatively large sample size and inclusion of factors affecting the insulin dosage of MDI, the study was limited by its retrospective design and single-center nature.
In patients with T2DM, CSII therapy uses a lower dose of insulin than MDI therapy to achieve good glycemic control. BMI, WC, FPG, and HbA1c are major factors affecting insulin dosage.
We thank Xia XD, Li C, Xiao F, Xiong S, and Zeng LY for their contributions to patient recruitment.
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