The outcome of frailty in older people with diabetes as a function of glycaemic control and hypoglycaemic therapy: a review

References

• Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and countacting insulin analogues have been shownry-level diabetes prevalence estimateacting insulin analogues have been shown for 2021 and projections for 2045. Diabet Res Clin Pract. 2022;183:109119. doi: 10.1016/j.diabres.2021.109119
   PubMed Web of Science ®Google Scholar
• Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabet Res Clin Pract. 2018;138:271–281. doi: 10.1016/j.diabres.2018.02.023
   PubMed Web of Science ®Google Scholar
• Sinclair AJ, Abdelhafiz AH, Rodríguez-Mañas L. Frailty and sarcopenia - newly emerging and high impact complications of diabetes. J Diabetes Complications. 2017;31(9):1465–1473. doi: 10.1016/j.jdiacomp.2017.05.003
   PubMed Web of Science ®Google Scholar
• Assar ME, Laosa O, Rodríguez Mañas L. Diabetes and frailty. Curr Opin Clin Nutr Metab Care. 2019;22(1):52–57. doi: 10.1097/MCO.0000000000000535
   PubMed Web of Science ®Google Scholar
• Bergman H, Ferrucci L, Guralnik J, et al. Frailty: An emerging research and clinical paradigm-issues and controversies. J Gerontol A Biol Sci Med Sci. 2009;62(7):731–737. doi: 10.1093/gerona/62.7.731
   Web of Science ®Google Scholar
• Sable-Morita S, Tanikawa T, Satake S, et al. Microvascular complications and frailty can predict adverse outcomes in older patients with diabetes. Geriatr Gerontol Int. 2021;21(4):359–363. doi: 10.1111/ggi.14142
   PubMed Web of Science ®Google Scholar
• UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837–853. doi: 10.1016/S0140-6736(98)07019-6
   PubMed Web of Science ®Google Scholar
• The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–2572. doi: 10.1056/NEJMoa0802987
   PubMed Web of Science ®Google Scholar
• The ACCORD Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–2559. doi: 10.1056/NEJMoa0802743
   PubMed Web of Science ®Google Scholar
• Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129–139. doi: 10.1056/NEJMoa0808431
   PubMed Web of Science ®Google Scholar
• Holman RR, Paul SK, Bethel MA, et al. 10-years follow-up of intensive glucose control in type 2 diabetes. N Eng J Med. 2008;359(15):1577–1589. doi: 10.1056/NEJMoa0806470
   PubMed Web of Science ®Google Scholar
• Abdelhafiz AH, Sinclair AJ. Cardio-renal protection in older people with diabetes with frailty and medical comorbidities-A focus on the new hypoglycaemic therapy. J Diabetes Complications. 2020;34(9):107639. doi: 10.1016/j.jdiacomp.2020.107639
   PubMed Web of Science ®Google Scholar
• MacKenzie HT, Tugwell B, Rockwood K, et al. Frailty and diabetes in older hospitalized adults: the case for routine frailty assessment. Can J Diabetes. 2020;44(3):241–245. doi: 10.1016/j.jcjd.2019.07.001
   PubMed Web of Science ®Google Scholar
• Chao CT, Wang J, Huang JW, et al. Cohort of GEriatric Nephrology in NTUH (COGENT) study group. Hypoglycemic episodes are associated with an increased risk of incident frailty among new onset diabetic patients. J Diabetes Complications. 2020;34(2):107492. doi: 10.1016/j.jdiacomp.2019.107492
   PubMedGoogle Scholar
• Yanagita I, Fujihara Y, Eda T, et al. Low glycated hemoglobin level is associated with severity of frailty in Japanese elderly diabetes patients. J Diabetes Investig. 2018;9(2):419–425. doi: 10.1111/jdi.12698
   PubMed Web of Science ®Google Scholar
• Morita T, Okuno T, Himeno T, et al. Glycemic control and disability-free survival in hypoglycemic agent-treated community-dwelling older patients with type 2 diabetes mellitus. Geriatr Gerontol Int. 2017;17(11):1858–1865. doi: 10.1111/ggi.12975
   PubMed Web of Science ®Google Scholar
• McAlister FA, Lethebe BC, Lambe C, et al. Control of glycemia and blood pressure in British adults with diabetes mellitus and subsequent therapy choices: a comparison across health states. Cardiovasc Diabetol. 2018;17(1):27. doi: 10.1186/s12933-018-0673-4
   PubMedGoogle Scholar
• Zaslavsky O, Walker RL, Crane PK, et al. Glucose Levels and Risk of Frailty. J Gerontol A Biol Sci Med Sci. 2016;71(9):1223–1229. doi: 10.1093/gerona/glw024
   PubMed Web of Science ®Google Scholar
• Kitamura A, Taniguchi Y, Seino S, et al. Combined effect of diabetes and frailty on mortality and incident disability in older Japanese adults. Geriatr Gerontol Int. 2019;19(5):423–428. doi: 10.1111/ggi.13637
   PubMed Web of Science ®Google Scholar
• Fung E, Lui LT, Huang L, et al. Characterising frailty, metrics of continuous glucose monitoring, and mortality hazards in older adults with type 2 diabetes on insulin therapy (HARE): a prospective, observational cohort study. Lancet Healthy Longev. 2021;2(11):e724–e735. doi: 10.1016/S2666-7568(21)00251-8
   PubMedGoogle Scholar
• Chung SM, Lee YH, Kim CO, et al. Daytime glycemic variability and frailty in older patients with diabetes: a pilot study using continuous glucose monitoring. J Korean Med Sci. 2021;36(27):e190. doi: 10.3346/jkms.2021.36.e190
   PubMed Web of Science ®Google Scholar
• Lin CL, Yu NC, Wu HC, et al. Risk factors associated with frailty in older adults with type 2 diabetes: A cross-sectional study. J Clin Nurs. 2022;31(7–8):967–974. doi: 10.1111/jocn.15953
   PubMed Web of Science ®Google Scholar
• Kong L, Zhao H, Fan J, et al. Predictors of frailty among Chinese community-dwelling older adults with type 2 diabetes: a cross-sectional survey. BMJ Open. 2021;11(3):e041578. doi: 10.1136/bmjopen-2020-041578
   PubMed Web of Science ®Google Scholar
• Bilgin S, Aktas G, Kurtkulagi O, et al. Edmonton frail score is associated with diabetic control in elderly type 2 diabetic subjects. J Diabetes Metab Disord. 2020;19(1):511–514. doi: 10.1007/s40200-020-00542-z
   PubMed Web of Science ®Google Scholar
• Hyde Z, Smith K, Flicker L, et al. HbA1c is associated with frailty in a group of aboriginal Australians. J Frailty Aging. 2019;8:17–20. doi: 10.14283/jfa.2018.41
   PubMed Web of Science ®Google Scholar
• García-Esquinas E, Graciani A, Guallar-Castillón P, et al. Diabetes and risk of frailty and its potential mechanisms: a prospective cohort study of older adults. J Am Med Dir Assoc. 2015;16(9):748–754. doi: 10.1016/j.jamda.2015.04.008
   PubMed Web of Science ®Google Scholar
• Aguayo GA, Hulman A, Vaillant MT, et al. Prospective association among diabetes diagnosis, HbA1c, Glycemia, and frailty trajectories in an elderly population. Diabetes Care. 2019;42(10):1903–1911. doi: 10.2337/dc19-0497
   PubMed Web of Science ®Google Scholar
• Ferri-Guerra J, Aparicio-Ugarriza R, Salguero D, et al. The association of frailty with hospitalizations and mortality among community dwelling older adults with diabetes. J Frailty Aging. 2020;9:94–100. doi: 10.14283/jfa.2019.31
   PubMed Web of Science ®Google Scholar
• Nguyen TN, Harris K, Woodward M, et al. The Impact of frailty on the effectiveness and safety of intensive glucose control and blood pressure–lowering therapy for people with type 2 diabetes: results from the ADVANCE trial. Diabetes Care. 2021;44(7):1622–1629. doi: 10.2337/dc20-2664
   PubMed Web of Science ®Google Scholar
• Huang C-F, Shiao M-S, Mao T-Y. Effects of low-dose metformin on pre-frailty among middle-aged and elderly pre-diabetic people. JCSM Rapid Comm. 2022;5(1):33–39. doi: 10.1002/rco2.55
   Google Scholar
• Baskaran D, Aparicio-Ugarriza R, Ferri-Guerra J, et al. Is there an association between metformin exposure and frailty? Gerontol Geriatr Med. 2020;6:2333721420924956. doi: 10.1177/2333721420924956
   Web of Science ®Google Scholar
• Wang CP, Lorenzo C, Habib SL, et al. Differential effects of metformin on age related comorbidities in older men with type 2 diabetes. J Diabetes Complications. 2017;31(4):679–686. doi: 10.1016/j.jdiacomp.2017.01.013
   PubMed Web of Science ®Google Scholar
• Sumantri S, Setiati S, Purnamasari D, et al. Relationship between metformin and frailty syndrome in elderly people with type 2 diabetes. Acta Med Indones. 2014;46(3):183–188.
   PubMedGoogle Scholar
• Wang CP, Lorenzo C, Espinoza SE. Frailty attenuates the impact of metformin on reducing mortality in older adults with type 2 diabetes. J Endocrinol Diabetes Obes. 2014;2(2):1031.
   PubMedGoogle Scholar
• Lee CG, Schwartz AV, Yaffe K, et al. Changes in physical performance in older women according to presence and treatment of diabetes mellitus. J Am Geriatr Soc. 2013;61(11):1872–1878. doi: 10.1111/jgs.12502
   PubMed Web of Science ®Google Scholar
• Hazuda HP, Pan Q, Florez H, et al. Association of intensive lifestyle and metformin interventions with frailty in the diabetes prevention program outcomes study. J Gerontol A Biol Sci Med Sci. 2021;76(5):929–936. doi: 10.1093/gerona/glaa295
   PubMed Web of Science ®Google Scholar
• Simpson FR, Justice JN, Pilla SJ, et al. An examination of whether diabetes control and treatments are associated with change in frailty index across 8 years: an ancillary exploratory study from the action for health in diabetes (Look AHEAD) trial. Diabetes Care. 2023;46(3):519–525. doi: 10.2337/dc22-1728
   PubMed Web of Science ®Google Scholar
• Liu P, Pan Y, Song Y, et al. Association of metformin exposure with low risks of frailty and adverse outcomes in patients with diabetes. Eur J Med Res. 2023;28(1):65. doi: 10.1186/s40001-023-01017-6
   PubMed Web of Science ®Google Scholar
• Mone P, Varzideh F, Jankauskas SS, et al. SGLT2 inhibition via empagliflozin improves endothelial function and reduces mitochondrial oxidative stress: insights from frail hypertensive and diabetic patients. Hypertension. 2022;79(8):1633–1643. doi: 10.1161/HYPERTENSIONAHA.122.19586
   PubMed Web of Science ®Google Scholar
• Abdelhafiz AH, Sinclair AJ. Cognitive frailty in older people with type 2 diabetes mellitus: the central role of hypoglycaemia and the need for prevention. Curr Diab Rep. 2019;19(4):15. PMID: 30806826. doi: 10.1007/s11892-019-1135-4
   PubMed Web of Science ®Google Scholar
• Abdelhafiz AH, Loo BE, Hensey N, et al. The U‐shaped relationship of traditional cardiovascular risk factors and adverse outcomes in later life. Aging Dis. 2012;3(6):454–464.
   PubMed Web of Science ®Google Scholar
• de Ruijter W, Westendorp RGJ, Assendelft WJJ, et al. Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study. BMJ. 2009;338(jan08 2):a3083. doi: 10.1136/bmj.a3083
   PubMedGoogle Scholar
• Yaffe K, Falvey CM, Hamilton N, et al. Health ABC Study. Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med. 2013;173(14):1300–1306. doi: 10.1001/jamainternmed.2013.6176
   PubMed Web of Science ®Google Scholar
• Srikanth V, Sinclair AJ, Hill-Briggs F, et al. Type 2 diabetes and cognitive dysfunction—towards effective management of both comorbidities. Lancet Diabetes Endocrinol. 2020;8(6):535–545. doi: 10.1016/S2213-8587(20)30118-2
   PubMed Web of Science ®Google Scholar
• Pansini A, Lombardi A, Morgante M, et al. Hyperglycemia and physical impairment in frail hypertensive older adults. Front Endocrinol. 2022;13:831556. doi: 10.3389/fendo.2022.831556
   PubMed Web of Science ®Google Scholar
• Mone P, De Gennaro S, Frullone S, et al. Hyperglycemia drives the transition from pre-frailty to frailty: the monteforte study. Eur J Intern Med. 2023 May;111:135–137.
   PubMed Web of Science ®Google Scholar
• Ida S, Kaneko R, Imataka K, et al. Relationship between frailty and mortality, hospitalization, and cardiovascular diseases in diabetes: a systematic review and meta-analysis. Cardiovasc Diabetol. 2019;18(1):81. doi: 10.1186/s12933-019-0885-2
   PubMed Web of Science ®Google Scholar
• Ting MJM, Hyde Z, Flicker L, et al. Associations between diabetes, body mass index and frailty: the western Australian health in men study. Maturitas. 2022 Jul;161:58–64.
   PubMed Web of Science ®Google Scholar
• Li H, Manwani B, Leng SX. Frailty, inflammation, and immunity. Aging Dis. 2011;2(6):466–473.
   PubMed Web of Science ®Google Scholar
• Pariser G, Hager K, Gillette P, et al. Active steps for diabetes: a community-campus partnership addressing frailty and diabetes. Diabetes Educ. 2014;40(1):60–67. doi: 10.1177/0145721713514281
   PubMed Web of Science ®Google Scholar
• Hoogendijk EO, Rijnhart JJM, Kowal P, et al. Socioeconomic inequalities in frailty among older adults in six low- and middle-income countries: results from the WHO Study on global AGEing and adult health (SAGE). Maturitas. 2018;115:56–63. doi: 10.1016/j.maturitas.2018.06.011
   PubMed Web of Science ®Google Scholar
• Wu Y, Xiong T, Tan X, et al. Frailty and risk of microvascular complications in patients with type 2 diabetes: a population-based cohort study. BMC Med. 2022;20(1):473. doi: 10.1186/s12916-022-02675-9
   PubMed Web of Science ®Google Scholar
• Abdelhafiz AH, Rodríguez-Mañas L, Morley JE, et al. Hypoglycemia in older people - a less well recognized risk factor for frailty. Aging Dis. 2015;6(2):156–167. doi: 10.14336/AD.2014.0330
   PubMed Web of Science ®Google Scholar
• Abdelhafiz AH, Emmerton D, Sinclair AJ. Impact of frailty metabolic phenotypes on the management of older people with type 2 diabetes mellitus. Geriatr Gerontol Int. 2021;21(8):614–622. doi: 10.1111/ggi.14214
   PubMed Web of Science ®Google Scholar
• Graham GG, Punt J, Arora M, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011;50(2):81–98. doi: 10.2165/11534750-000000000-00000
   PubMed Web of Science ®Google Scholar
• Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl). 2011;89(7):667–676. doi: 10.1007/s00109-011-0748-0
   PubMed Web of Science ®Google Scholar
• Abdelhafiz AH, Davies PC, Sinclair AJ. Triad of impairment in older people with diabetes-reciprocal relations and clinical implications. Diabet Res Clin Pract. 2020;161:108065. doi: 10.1016/j.diabres.2020.108065
   PubMed Web of Science ®Google Scholar
• Gore DC, Wolf SE, Sanford A, et al. Influence of metformin on glucose intolerance and muscle catabolism following severe burn injury. Ann Surg. 2005;241(2):334–342. doi: 10.1097/01.sla.0000152013.23032.d1
   PubMed Web of Science ®Google Scholar
• Esteghamati A, Eskandari D, Mirmiranpour H, et al. Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: a randomized clinical trial. Clin Nutr. 2013;32(2):179–185. doi: 10.1016/j.clnu.2012.08.006
   PubMed Web of Science ®Google Scholar
• Espinoza SE, Musi N, Wang CP, et al. Rationale and study design of a randomized clinical trial of metformin to prevent frailty in older adults with prediabetes. J Gerontol A Biol Sci Med Sci. 2020;75(1):102–109. doi: 10.1093/gerona/glz078
   PubMed Web of Science ®Google Scholar
• Mone P, Martinelli G, Lucariello A, et al. Extended-release metformin improves cognitive impairment in frail older women with hypertension and diabetes: preliminary results from the LEOPARDESS Study. Cardiovasc Diabetol. 2023;22(1):94. doi: 10.1186/s12933-023-01817-4
   PubMed Web of Science ®Google Scholar
• Mone P, Lombardi A, Gambardella J, et al. Empagliflozin improves cognitive impairment in frail older adults with type 2 diabetes and heart failure with preserved ejection fraction. Diabetes Care. 2022;45(5):1247–1251. doi: 10.2337/dc21-2434
   PubMed Web of Science ®Google Scholar
• Mone P, Gambardella J, Lombardi A, et al. Correlation of physical and cognitive impairment in diabetic and hypertensive frail older adults. Cardiovasc Diabetol. 2022;21(1):10. doi: 10.1186/s12933-021-01442-z
   PubMed Web of Science ®Google Scholar
• Vaidya AR, Wolska N, Vara D, et al. Diabetes and thrombosis: a central role for vascular oxidative stress. Antioxidants. 2021;10(5):706. doi: 10.3390/antiox10050706
   Web of Science ®Google Scholar
• Alabadi B, Civera M, De la Rosa A, et al. Frailty is associated with oxidative stress in older patients with type 2 diabetes. Nutrients. 2021;13(11):3983. doi: 10.3390/nu13113983
   PubMed Web of Science ®Google Scholar
• Bernabeu-Wittel M, Gómez-Díaz R, González-Molina Á, et al. On behalf of the proteo researchers. Oxidative stress, telomere shortening, and apoptosis associated to sarcopenia and frailty in patients with multimorbidity. J Clin Med. 2020;9(8):E2669. doi: 10.3390/jcm9082669
   PubMed Web of Science ®Google Scholar
• Mone P, Lombardi A, Kansakar U, et al. Empagliflozin improves the MicroRNA signature of endothelial dysfunction in patients with heart failure with preserved ejection fraction and diabetes. J Pharmacol Exp Ther. 2023;384(1):116–122. doi: 10.1124/jpet.121.001251
   PubMed Web of Science ®Google Scholar
• Butt JH, Dewan P, Merkely B, et al. Efficacy and safety of dapagliflozin according to frailty in heart failure with reduced ejection fraction: a post hoc analysis of the DAPA-HF Trial. Ann Intern Med. 2022;175(6):820–830. doi: 10.7326/M21-4776
   PubMed Web of Science ®Google Scholar
• Lv X, Dong Y, Hu L, et al. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the management of nonalcoholic fatty liver disease (NAFLD): A systematic review. Endocrinol Diabetes Metab. 2020;3(3):e00163. doi: 10.1002/edm2.163
   PubMedGoogle Scholar
• Zhang X, Bai R, Jia Y, et al. The effect of liraglutide on nonalcoholic fatty liver disease in type 2 diabetes mellitus. Int J Diabetes Dev Ctries. 2020;40(4):491–499. doi: 10.1007/s13410-020-00857-w
   Web of Science ®Google Scholar
• Feig DI, Kang D-H, Johnson rj. uric Acid and Cardiovascular Risk. N Engl J Med. 2008;359(17):1811–1821. doi: 10.1056/NEJMra0800885
   PubMed Web of Science ®Google Scholar
• Fujimoto K, Iwakura T, Aburaya M, et al. Twice-daily insulin degludec/insulin aspart effectively improved morning and evening glucose levels and quality of life in patients previously treated with premixed insulin: An observational study. Diabetol Metab Syndr. 2018;10(1):1–8. doi: 10.1186/s13098-018-0366-x
   PubMedGoogle Scholar
• Bradley MC, Chillarige Y, Lee H, et al. Severe hypoglycemia risk with long-acting insulin analogs vs neutral protamine hagedorn insulin. JAMA Intern Med. 2021;181(5):598. doi: 10.1001/jamainternmed.2020.9176
   PubMed Web of Science ®Google Scholar
• Betônico CC, Titan SMO, Lira A, et al. Insulin glargine U100 improved glycemic control and reduced nocturnal hypoglycemia in patients with type 2 diabetes mellitus and chronic kidney disease stages 3 and 4. Clin Ther. 2019;41(10):2008–2020.e3. doi: 10.1016/j.clinthera.2019.07.011
   PubMed Web of Science ®Google Scholar
• Zçelik S, Çelik M, Vural A, et al. Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: A real-world experience. Arch Med Sci. 2021;17(1):1–8. doi: 10.5114/aoms.2020.93264
   PubMed Web of Science ®Google Scholar
• Tamura Y, Omura T, Toyoshima K, et al. Nutrition management in older adults with diabetes: a review on the importance of shifting prevention strategies from metabolic syndrome to frailty. Nutrients. 2020;12(11):3367. doi: 10.3390/nu12113367
   PubMed Web of Science ®Google Scholar
• Dunning T, Sinclair A, Colagiuri S. New IDF Guideline for managing type 2 diabetes in older people. Diabet Res Clin Pract. 2014;103(3):538–540. doi: 10.1016/j.diabres.2014.03.005
   PubMed Web of Science ®Google Scholar
• LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520–1574. doi: 10.1210/jc.2019-00198
   PubMed Web of Science ®Google Scholar
• Hambling CE, Khunti K, Cos X, et al. Factors influencing safe glucose-lowering in older adults with type 2 diabetes: A PeRsOn-centred ApproaCh to IndiVidualisEd (PROACTIVE) glycemic goals for older people: a position statement of prim care diabetes Europe. Prim Care Diabetes. 2019;13(4):330–352. doi: 10.1016/j.pcd.2018.12.005
   PubMed Web of Science ®Google Scholar
• Sinclair AJ, Abdelhafiz A, Dunning T, et al. An international position statement on the management of frailty in diabetes mellitus: summary of recommendations 2017. J Frailty Aging. 2018;7(1):10–20. doi: 10.14283/jfa.2017.39
   PubMed Web of Science ®Google Scholar
• Cosentino F, Grant PJ, Aboyans V. The task force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255–323. doi: 10.1093/eurheartj/ehz486
   PubMed Web of Science ®Google Scholar
• Bollig C, Torbahn G, Bauer J, et al. Evidenzmangel für die antihyperglykämische Pharmakotherapie gebrechlicher älterer Patienten. Z Gerontol Geriat. 2020;54(3):278–284. doi: 10.1007/s00391-020-01724-3
   PubMedGoogle Scholar
• Sjöblom P, Tengblad A, Löfgren UB, et al. Can diabetes medication be reduced in elderly patients? An observational study of diabetes drug withdrawal in nursing home patients with tight glycaemic control. Dib Res Clin Pract. 2008;82(2):197–202. doi: 10.1016/j.diabres.2008.08.014
   PubMed Web of Science ®Google Scholar
• Abdelhafiz AH, Chakravorty P, Gupta S, et al. Can hypoglycaemic medications be withdrawn in older people with type 2 diabetes? Int J Clin Pract. 2014;68(6):790–792. doi: 10.1111/ijcp.12455
   PubMedGoogle Scholar
• Aversa A, Monzani F, La Vignera S. Editorial: endocrine frailty in the elderly. Front Endocrinol. 2019 Sep 11;10:627. doi: 10.3389/fendo.2019.00627
   PubMed Web of Science ®Google Scholar
• CaMos Research Group, Li G, Prior JC, Leslie WD, et al. Frailty and risk of fractures in patients with type 2 diabetes. Diabetes Care. 2019;42(4):507–513.
   PubMed Web of Science ®Google Scholar
• Sanz-Cánovas J, López-Sampalo A, Cobos-Palacios L, et al. Management of type 2 diabetes mellitus in elderly patients with frailty and/or sarcopenia. Int J Environ Res Public Health. 2022;19:8677. doi: 10.3390/ijerph19148677
   PubMedGoogle Scholar
• Paterni S, Okoye C, Calabrese AM, et al. Prognostic value of glycated hemoglobin in frail older diabetic patients with hip fracture. Front Endocrinol. 2021;12:770400. doi: 10.3389/fendo.2021.770400
   PubMed Web of Science ®Google Scholar
• Forbes A. Reducing the burden of mortality in older people with diabetes: a review of current research. Front Endocrinol. 2020;11:133. doi: 10.3389/fendo.2020.00133
   PubMed Web of Science ®Google Scholar
• Shi J, Tao Y, Wang L, et al. Combined effect of diabetes and frailty on mortality among Chinese older adults: A follow-up study. Front Endocrinol. 2023;13:1105957. doi: 10.3389/fendo.2022.1105957
   PubMed Web of Science ®Google Scholar
• Dent E, Martin FC, Bergman H, et al. Management of frailty: opportunities, challenges, and future directions. Lancet. 2019;394(10206):1376–1386. doi: 10.1016/S0140-6736(19)31785-4
   PubMed Web of Science ®Google Scholar
• Ahlqvist E, Storm P, Käräjämäki A, et al. Novel subgroups of adult- onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018;6(5):361–369. doi: 10.1016/S2213-8587(18)30051-2
   PubMed Web of Science ®Google Scholar
• Castrejón-Pérez RC, Gutiérrez-Robledo LM, Cesari M, et al. Diabetes mellitus, hypertension and frailty: A population-based, cross-sectional study of Mexican older adults. Geriatr Gerontol Int. 2017;17(6):925–930. doi: 10.1111/ggi.12805
   PubMed Web of Science ®Google Scholar
• Becker C, Lord SR, Studenski SA, et al. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol. 2015;3(12):948–957. doi: 10.1016/S2213-8587(15)00298-3
   PubMed Web of Science ®Google Scholar
• Makimura H, Feldpausch MN, Rope AM, et al. Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial. J Clin Endocrinol Metab. 2012;97(12):4769–4779. doi: 10.1210/jc.2012-2794
   PubMed Web of Science ®Google Scholar
• Marty E, Liu Y, Samuel A, et al. A review of sarcopenia: enhancing awareness of an increasingly prevalent disease. Bone. 2017;105:276–286. doi: 10.1016/j.bone.2017.09.008
   PubMed Web of Science ®Google Scholar
• Sakkiah S, Ng HW, Tong W, et al. Structures of androgen receptor bound with ligands: advancing understanding of biological functions and drug discovery. Expert Opin Ther Targets. 2016;20(10):1267–1282. doi: 10.1080/14728222.2016.1192131
   PubMed Web of Science ®Google Scholar
• Dalton JT, Barnette KG, Bohl CE, et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011;2(3):153–1561. doi: 10.1007/s13539-011-0034-6
   PubMed Web of Science ®Google Scholar
• Sinclair AJ, Abdelhafiz AH. Metabolic impact of frailty changes diabetes trajectory. Metabolites. 2023;13(2):295. doi: 10.3390/metabo13020295
   PubMed Web of Science ®Google Scholar
• Bajaj HS, Bergenstal RM, Christoffersen A, et al. Switching to Once-weekly insulin icodec versus once-daily insulin glargine U100 in type 2 diabetes inadequately controlled on daily basal insulin: a phase 2 randomized controlled trial. Diabetes Care. 2021;44(7):1586–1594. doi: 10.2337/dc20-2877
   PubMed Web of Science ®Google Scholar
• Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol. 2014;2(10):819–829. doi: 10.1016/S2213-8587(14)70034-8
   PubMed Web of Science ®Google Scholar
• Yanase T, Yanagita I, Muta K, et al. Frailty in elderly diabetes patients. Endocr J. 2018;65(1):1–11. doi: 10.1507/endocrj.EJ17-0390
   PubMed Web of Science ®Google Scholar
• Mielke N, Schneider A, Huscher D, et al. Gender differences in frailty transition and its prediction in community-dwelling old adults. Sci Rep. 2022;12(1):7341. doi: 10.1038/s41598-022-11358-7
   PubMed Web of Science ®Google Scholar
• Sherifali D. Diabetes and frailty: revisiting the converging conditions. Can J Diabetes. 2019;43(2):81. doi: 10.1016/j.jcjd.2019.01.006
   PubMed Web of Science ®Google Scholar
• Assar ME, Angulo J, Rodríguez-Mañas L. Diabetes and ageing-induced vascular inflammation. J Physiol. 2016;594(8):2125–2146. doi: 10.1113/JP270841
   PubMed Web of Science ®Google Scholar