Insulin in Frail, Older People with Type 2 Diabetes—Low Threshold for Therapy
Abstract
:1. Introduction
2. Methods
3. Effects of Insulin on Skeletal Muscles
4. Insulin Analogues Safety
5. Insulin—Low Threshold of Therapy
6. Insulin Use in Frail, Older People with Diabetes
7. Goals of Therapy
8. Future Perspectives
9. Conclusions
10. Key Points
- Frailty and sarcopenia are newly emerged diabetes-related complications in older people with diabetes.
- Frailty appears to be metabolically heterogeneous with anorexic malnourished (AM) phenotypes at one end, and sarcopenic obese (SO) phenotypes at the other end of the spectrum.
- The AM phenotype is likely to be less tolerant to oral hypoglycaemic therapy due to multiple comorbidities and organ dysfunction.
- Insulin therapy, especially long-acting insulin analogues, are an early option in the AM phenotype.
- Insulin may have positive effects on muscle function in this frail phenotype, although future confirmation studies are required.
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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---|---|---|---|
Tanaka K et al., cross-sectional, Japan, 2015 [9]. | 191 men with type 2 DM, mean (SD) age 60.2 (12.5) Y. | Examine association of muscle mass with endogenous insulin secretion. | A. Endogenous insulin significantly and positively correlated with muscle mass of arms and legs as well as RSMI (p < 0.05). B. Endogenous insulin significantly lower in subjects with compared to those without sarcopenia (p < 0.05). |
Bouchi R et al., retrospective observational, Japan, 2017 [10]. | 312 patients with type 2 DM, mean (SD) age 64.0 (11.0) Y. | Examine impact of insulin treatment on muscle mass. | A. Insulin was protective against annual decline in SMI (standardized β 0.195; p = 0.025) adjusted for covariates. B. In a cohort matched by propensity scores, insulin significantly increased the 1-year change in SMI compared with non-insulin-treated group; mean (SE) 2.40 (0.98%) vs. −0.43 (0.98%), p = 0.050). |
Cui M et al., cross-sectional, China, 2020 [12]. | 132 patients with type 2 DM, aged ≥65 Y. | Explore factors associated with sarcopenia. | A. Insulin use was not significantly different between patients with sarcopenia and those with no sarcopenia (68.4% vs. 74.5%, p = 0.48). B. Metformin was significantly less used in patients with compared to those with no sarcopenia (13.2% vs. 41.5%, p = 0.002). |
Ferrari U et al., prospective, Germany, 2020 [13]. | 731 (118 type 2 DM) participants of KORA-Age study, mean (SD) age 74.6 (6.2) Y, F/UP 3 Y. | Investigate association of type 2 DM and insulin treatment with changes in muscle mass, muscle strength and physical performance. | A. DM associated with change in SMI (β −0.1 (95% CI −0.3 to −0.02) kg/m2, p = 0.02), but not with a change in GS (β −0.9, 95% CI −1.9 to 0.04 kg) or TUG (β −0.1, 95% CI −0.7 to 0.5 s). B. Insulin therapy positively associated with change in SMI (β 0.6 (95% CI 0.3 to 0.9) kg/m2, p = 0.001), but not in GS (β −1.6, 95% CI −4.1 to 0.8 kg) or TUG (β 1.6, 95% CI −0.2 to 3.4 s). |
Sugimoto K et al., observational longitudinal, Japan, 2021 [14]. | 588 patients with type 2 DM, mean (SD) age 70.0 (8.0) Y, F/U 1Y. | Examine relationship between glycaemic control and effect of antidiabetic agents on sarcopenia. | After 382 (53) days of F/U: A. Frequency of sarcopenia non-significantly increased (7.8% vs. 6.3%, p = 0.12). B. Patients with ≥1% drop in HbA1c had significant increase in SMI (B = 0.113, p = 0.027), gait speed (B = 0.145, p = 0.002), but non-significant change in handgrip strength (B = −0.005, p = 0.914). C. Insulin use significantly increased SMI (B = 0.115, p = 0.022). D. Oral antidiabetic therapy has no effect on sarcopenia. |
Study | Patients | Aim to | Main Findings |
---|---|---|---|
Fujimoto K. et al., prospective, observational, Japan, 2018 [23]. | 22 patients with type 2 DM, mean (SD) age 68.0 (9.9) Y, treated with premixed insulin for 2 M, then IDegAsp for next 2 M. | Investigate changes in glucose variability and QOL during switch from premixed insulin to IDegAsp twice daily. | Switching to IDegAsp from premixed insulin: A. Improved daily glucose level variability, morning and evening glucose control and QOL. B. No change in day-to-day variability of morning fasting glucose levels. |
Lipska KJ et al., retrospective observational, US, 2018 [24]. | 25,489 patients with type 2 DM initiated basal or NPH insulin, mean (SD) age 60.2 (11.8) Y. F/Up 1.7Y. | Compare rates of hypoglycaemia-related ED visits or hospitalisation associated with initiation of long-acting insulin analogues vs. NPH insulin. | A. In 1928 patients initiated on insulin analogue, there were 39 hypoglycaemia-related ED visits or hospital admissions (11.9 events, 95% CI 8.1 to 15.6/1000 person–years) compared with 354 events among 23,561 patients on NPH (8.8 events, 7.9 to 9.8/1000 person–years, p = 0.07). B. Adjusted HR 1.16, 95% CI, 0.71 to 1.78 for hypoglycaemia-related events with insulin analogue use. C. After one year, there was no significant difference in glycaemic control between both groups. |
Bradley MC et al., retrospective, US, 2021 [27]. | Medicare 575, 008 patients, mean (SD) age 74.9 (6.7) Y with type 2 DM, 407,018 initiated insulin glargine, 141,588 detemir, 26,402 NPH. | Examine risk of ED visits or hospitalisations due to hypoglycaemia in older community patients with type 2 DM who initiated long acting or NPH insulin. | A. Incidence rates for ED visits or hospitalisations for hypoglycaemia per 1000 person–years were 17.37 (95% CI 16.89 to17.84) for glargine and 26.64 (95% CI 26.01–27.3) for NPH. B. For detemir and NPH, incidence rates were 16.69 (15.92 to 17.51) and 25.04 (24.01 to 26.11), respectively. C. Glargine or detemir use associated with reduced risk of hypoglycaemia compared with NPH (HR for glargine vs. NPH 0.71, 95% CI 0.63 to 0.80, and detemir vs. NPH insulin 0.72, 0.63 to 0.82). |
Betônico CC et al., prospective, randomized, 2-way, crossover, open-label, Brazil, 2019 [28]. | 34 patients with type 2 DM randomly assigned to glargine U100 {16 patients, mean (SD) age 63.0 (7.0) Y} or NPH {18 patients, mean (SD) age 60.0 (8.7) Y}. | Compare glycaemic response to glargine U100 or NPH in patients with type 2 DM and CKD stages 3 and 4. | A. After 24 weeks, mean HbA1c declined from 8.86% (72.7 mmol/mol) to 7.95% (62.8 mmol/mol) in glargine group, but increased from 8.21% (66.2 mmol/mol) to 8.44% (69.4 mmol/mol) in INPH group, p = 0.029. B. Incidence of nocturnal hypoglycaemia was 3 times lower with glargine (0.5 events/patient) than with INPH (1.5 events/patient; p = 0.047). |
Ozcelik et al., prospective observational, Turkey, 2021 [30]. | 115 patients with type 2 DM, group 1, 55 on premixed insulin switched to IDegAsp; group 2, 60 on intensive insulin switched to bd IDegAsp, median (IQR) age 67.0 (62.0–69.0). Y. | Evaluate efficacy and safety of transition from premixed and intensive insulin to twice-daily insulin IDegAsp. | A. Mean (SD) rate hypoglycaemia 1.5 (0.85)/week before treatment switch in group 1 decreased to 0.03 (0.11)/week after IdegAsp (p < 0.0001). B. In group 2, episodes of hypoglycaemia were 0.93 (1.17)/week before treatment transition, decreased to 0.07 (0.25)/week after IDegAsp (p < 0.0001). |
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Abdelhafiz, A.; Bisht, S.; Kovacevic, I.; Pennells, D.; Sinclair, A. Insulin in Frail, Older People with Type 2 Diabetes—Low Threshold for Therapy. Diabetology 2022, 3, 369-383. https://doi.org/10.3390/diabetology3020028
Abdelhafiz A, Bisht S, Kovacevic I, Pennells D, Sinclair A. Insulin in Frail, Older People with Type 2 Diabetes—Low Threshold for Therapy. Diabetology. 2022; 3(2):369-383. https://doi.org/10.3390/diabetology3020028
Chicago/Turabian StyleAbdelhafiz, Ahmed, Shail Bisht, Iva Kovacevic, Daniel Pennells, and Alan Sinclair. 2022. "Insulin in Frail, Older People with Type 2 Diabetes—Low Threshold for Therapy" Diabetology 3, no. 2: 369-383. https://doi.org/10.3390/diabetology3020028