Insulin resistance in type 1 diabetes
Keywords:
Type 1 diabetes, insulin resistance, vascular complication, double diabetesAbstract
During recent years, the condition whereby insulin resistance and type 1 diabetes combine, namely Double Diabetes, has become more widely recognised by scientific communities, in line with the increasing prevalence of obesity among populations with type 1 diabetes. Ample evidence shows that insulin resistance plays an important role in the increased risk of vascular complications, independent of glycaemic control. Given the increased prevalence of individuals with features of double diabetes, pragmatic diagnostic criteria are paramount. In this review, we discuss the potential role of estimated glucose disposal rate as an assessment of insulin resistance for individuals with type 1 diabetes. We also discuss the challenges of managing insulin resistance given that factors including peripheral insulin administration and fear of hypoglycaemic impede weight management in this group. Non-insulin therapy such as sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists may also have an additional role in improving insulin resistance but more studies on this topic are required before drawing any robust conclusion.
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References
Teupe B, Bergis K. Epidemiological evidence for "double diabetes". Lancet 1991;337(8737):361-2.
Thorn LM, Forsblom C, Waden J, Soderlund J, Rosengard-Barlund M, Saraheimo M, et al. Effect of parental type 2 diabetes on offspring with type 1 diabetes. Diabetes Care 2009;32(1):63-8.
Purnell JQ, Dev RK, Steffes MW, Cleary PA, Palmer JP, Hirsch IB, et al. Relationship of family history of type 2 diabetes, hypoglycemia, and autoantibodies to weight gain and lipids with intensive and conventional therapy in the Diabetes Control and Complications Trial. Diabetes 2003;52(10):2623-9.
Erbey JR, Kuller LH, Becker DJ, Orchard TJ. The association between a family history of type 2 diabetes and coronary artery disease in a type 1 diabetes population. Diabetes Care 1998;21(4):610-4.
Roglic G, Colhoun HM, Stevens LK, Lemkes HH, Manes C, Fuller JH. Parental history of hypertension and parental history of diabetes and microvascular complications in insulin-dependent diabetes mellitus: the EURODIAB IDDM Complications Study. Diabetic Medicine: a Journal of the British Diabetic Association 1998;15(5):418-26.
Gingras V, Leroux C, Fortin A, Legault L, Rabasa-Lhoret R. Predictors of cardiovascular risk among patients with type 1 diabetes: a critical analysis of the metabolic syndrome and its components. Diabetes & Metabolism 2017;43(3):217-22.
Thorn LM, Forsblom C, Waden J, Saraheimo M, Tolonen N, Hietala K, et al. Metabolic syndrome as a risk factor for cardiovascular disease, mortality, and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care 2009;32(5):950-2.
Davis TM, Bruce DG, Davis WA. Prevalence and prognostic implications of the metabolic syndrome in community-based patients with type 1 diabetes: the Fremantle Diabetes Study. Diabetes Research and Clinical Practice 2007;78(3):412-7.
Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ. Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes 2000;49(4):626-32.
Epstein EJ, Osman JL, Cohen HW, Rajpathak SN, Lewis O, Crandall JP. Use of the estimated glucose disposal rate as a measure of insulin resistance in an urban multiethnic population with type 1 diabetes. Diabetes Care 2013;36(8):2280-5.
Nystrom T, Holzmann MJ, Eliasson B, Svensson AM, Sartipy U. Estimated glucose disposal rate predicts mortality in adults with type 1 diabetes. Diabetes, Obesity & Metabolism 2018;20(3):556-63.
Orchard TJ, Chang YF, Ferrell RE, Petro N, Ellis DE. Nephropathy in type 1 diabetes: a manifestation of insulin resistance and multiple genetic susceptibilities? Further evidence from the Pittsburgh Epidemiology of Diabetes Complication Study. Kidney International 2002;62(3):963-70.
Olson JC, Erbey JR, Forrest KY, Williams K, Becker DJ, Orchard TJ. Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity arterial disease events in type 1 diabetes. Metabolism: Clinical and Experimental 2002;51(2):248-54.
Orchard TJ, Olson JC, Erbey JR, Williams K, Forrest KY, Smithline Kinder L, et al. Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 2003;26(5):1374-9.
Pambianco G, Costacou T, Orchard TJ. The prediction of major outcomes of type 1 diabetes: a 12-year prospective evaluation of three separate definitions of the metabolic syndrome and their components and estimated glucose disposal rate: the Pittsburgh Epidemiology of Diabetes Complications Study experience. Diabetes Care 2007;30(5):1248-54.
Cleland SJ. Cardiovascular risk in double diabetes mellitus--when two worlds collide. Nature Reviews Endocrinology 2012;8(8):476-85.
Kietsiriroje N, Pearson S, Campbell M, Ariëns RAS, Ajjan RA. Double diabetes: a distinct high-risk group? Diabetes, Obesity and Metabolism 2019;21(12):2609-18.
Pozzilli P, Buzzetti R. A new expression of diabetes: double diabetes. Trends in Endocrinology and Metabolism 2007;18(2):52-7.
Dabelea D, D’Agostino RB, Mason CC, West N, Hamman RF, Mayer-Davis EJ, et al. Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study. Diabetologia 2010;54(1):78-86.
Duca LM, Maahs DM, Schauer IE, Bergman BC, Nadeau KJ, Bjornstad P, et al. Development and validation of a method to 20. estimate insulin sensitivity in patients with and without type 1 diabetes. Journal of Clinical Endocrinology & Metabolism 2016;101(2):686-95.
Cano A, Llauradó G, Albert L, Mazarico I, Astiarraga B, González-Sastre M, et al. Utility of insulin resistance in estimating cardiovascular risk in subjects with type 1 diabetes according to the scores of the steno type 1 risk engine. Journal of Clinical Medicine 2020; 9(7):2192.
Linn W, Persson M, Rathsman B, Ludvigsson J, Lind M, Andersson Franko M, et al. Estimated glucose disposal rate is associated with retinopathy and kidney disease in young people with type 1 diabetes: a nationwide observational study. Cardiovascular Diabetology 2023;22(1):61.
Merger SR, Kerner W, Stadler M, Zeyfang A, Jehle P, Muller-Korbsch M, et al. Prevalence and comorbidities of double diabetes. Diabetes Research and Clinical Practice 2016;119:48-56.
Helliwell R, Warnes H, Kietsiriroje N, Campbell M, Birch R, Pearson SM, et al. Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: beyond glycated haemoglobin. Diabetic Medicine: a Journal of the British Diabetic Association 2021;38(5):e14529.
Miller RG, Costacou T. Cardiovascular disease in adults with type 1 diabetes: looking beyond glycemic control. Current Cardiology Reports 2022;24(10):1467-75.
Miller RG, Orchard TJ, Costacou T. 30-year cardiovascular disease in type 1 diabetes: risk and risk factors differ by long-term patterns of glycemic control. Diabetes Care 2022;45(1):142-50.
Conway B, Miller RG, Costacou T, Fried L, Kelsey S, Evans RW, et al. Temporal patterns in overweight and obesity in Type 1 diabetes. Diabetic Medicine: a Journal of the British Diabetic Association 2010;27(4):398-404.
Van der Schueren B, Ellis D, Faradji RN, Al-Ozairi E, Rosen J, Mathieu C. Obesity in people living with type 1 diabetes. Lancet Diabetes & Endocrinology 2021;9(11):776-85.
Dejkhamron P, Santiprabhob J, Likitmaskul S, Deerochanawong C, Rawdaree P, Tharavanij T, et al. Type 1 diabetes management and outcomes: a multicenter study in Thailand. J Diabetes Investig 2021;12(4):516-26.
+1
Foster NC, Beck RW, Miller KM, Clements MA, Rickels MR, DiMeglio LA, et al. State of type 1 diabetes management and outcomes from the T1D exchange in 2016-2018. Diabetes Technology & Therapeutics 2019;21(2):66-72.
Jirawatwarakul T, Pruktanakul T, Churuangsuk C, Aunjitsakul W, Tsutsumi WD, Leelawattana R, et al. Progression of insulin resistance in individuals with type 1 diabetes: a retrospective longitudinal study on individuals from Thailand. Diabetes and Vascular Disease Research 2023;20(6):14791641231221202.
De Keukelaere M, Fieuws S, Reynaert N, Vandoorne E, Kerckhove KV, Asscherickx W, et al. Evolution of body mass index in children with type 1 diabetes mellitus. European Journal of Pediatrics 2018;177(11):1661-6.
Saelens BE, Sallis JF, Frank LD, Couch SC, Zhou C, Colburn T, et al. Obesogenic neighborhood environments, child and parent obesity: the Neighborhood Impact on Kids study. American Journal of Preventive Medicine 2012;42(5):e57-64.
Edgerton DS, Moore MC, Winnick JJ, Scott M, Farmer B, Naver H, et al. Changes in glucose and fat metabolism in response to the administration of a hepato-preferential insulin analog. Diabetes 2014;63(11):3946-54.
Donga E, Dekkers OM, Corssmit EP, Romijn JA. Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis. European Journal of Endocrinology 2015;173(1):101-9.
Hother-Nielsen O, Schmitz O, Bak J, Beck-Nielsen H. Enhanced hepatic insulin sensitivity, but peripheral insulin resistance in patients with type 1 (insulin-dependent) diabetes. Diabetologia 1987;30(11):834-40.
Martyn-Nemeth P, Quinn L, Penckofer S, Park C, Hofer V, Burke L. Fear of hypoglycemia: influence on glycemic variability and self-management behavior in young adults with type 1 diabetes. Journal of Diabetes and Its Complications 2017;31(4):735-41.
+1
Alobaid AM, Zulyniak MA, Ajjan RA, Broz J, Hopkins M, Campbell MD. Barriers to exercise in adults with type 1 diabetes and insulin resistance. Can J Diabetes 2023;47(6):503-8.
Mao Y, Zhong W. Changes of insulin resistance status and development of complications in type 1 diabetes mellitus: Analysis of DCCT/EDIC study. Diabetes Research and Clinical Practice 2022;184:109211.
Riddell MC, Gallen IW, Smart CE, Taplin CE, Adolfsson P, Lumb AN, et al. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes & Endocrinology 2017;5(5):377-90.
Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KHK, MacLeod J, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care 2019;42(5):731-54.
Kietsiriroje N, Shah H, Zare M, O’Mahoney LL, West DJ, Pearson SM, et al. Dietary fat intake is associated with insulin resistance and an adverse vascular profile in patients with T1D: a pooled analysis. European Journal of Nutrition 2023:62(3):1231-8.
Alobaid AM, Dempsey PC, Francois M, Zulyniak MA, Hopkins M, Campbell MD. Reducing sitting time in type 1 diabetes: considerations and implications. Can J Diabetes 2023;47(3):300-4.
Campbell MD, Alobaid AM, Hopkins M, Dempsey PC, Pearson SM, Kietsiriroje N, et al. Interrupting prolonged sitting with frequent short bouts of light-intensity activity in people with type 1 diabetes improves glycaemic control without increasing hypoglycaemia: The SITLESS randomised controlled trial. Diabetes, Obesity and Metabolism 2023;25(12):3589-98.
Petrie JR, Chaturvedi N, Ford I, Brouwers MCGJ, Greenlaw N, Tillin T, et al. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes & Endocrinology 2017;5(8):597-609.
Warnes H, Helliwell R, Pearson SM, Ajjan RA. Metabolic control in type 1 diabetes: is adjunctive therapy the way forward? Diabetes Therapy: Research, Treatment and Education of Diabetes and Related Disorders 2018;9(5):1831-51.
Mathieu C, Zinman B, Hemmingsson JU, Woo V, Colman P, Christiansen E, et al. Efficacy and safety of liraglutide added to insulin treatment in type 1 diabetes: The Adjunct One Treat-To-Target Randomized Trial. Diabetes Care 2016;39(10):1702-10.
Ahrén B, Hirsch IB, Pieber TR, Mathieu C, Gómez-Peralta F, Hansen TK, et al. Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes: the adjunct two randomized trial. Diabetes Care 2016;39(10):1693-701.
Dandona P, Mathieu C, Phillip M, Hansen L, Griffen SC, Tschöpe D, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes & Endocrinology 2017;5(11):864-76.
Mathieu C, Dandona P, Gillard P, Senior P, Hasslacher C, Araki E, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 24-week results from a randomized controlled trial. Diabetes Care 2018;41(9):1938-46.
Rosenstock J, Marquard J, Laffel LM, Neubacher D, Kaspers S, Cherney DZ, et al. Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: the EASE Trials. Diabetes Care 2018;41(12):2560-9.
Buse JB, Garg SK, Rosenstock J, Bailey TS, Banks P, Bode BW, et al. Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: the North American inTandem1 Study. Diabetes Care 2018;41(9):1970-80.
Danne T, Cariou B, Banks P, Brandle M, Brath H, Franek E, et al. HbA1c and hypoglycemia reductions at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 Study. Diabetes Care 2018;41(9):1981-90.
Garg SK, Henry RR, Banks P, Buse JB, Davies MJ, Fulcher GR, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. New England Journal of Medicine 2017;377(24):2337-48.
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