Skip to main content
Top
Published in: Diabetes Therapy 1/2018

Open Access 01-02-2018 | Review

A Review of Insulin Resistance in Type 1 Diabetes: Is There a Place for Adjunctive Metformin?

Authors: Gagan Priya, Sanjay Kalra

Published in: Diabetes Therapy | Issue 1/2018

Login to get access

Abstract

There is a rising trend of overweight and obesity among individuals with type 1 diabetes. This is often associated with insulin resistance, increased insulin dose requirements and poor glycemic control. Insulin resistance is also seen during puberty and is strongly related to increased risk of cardiovascular disease. The role of metformin as an adjunct to ongoing intensive insulin therapy in type 1 diabetics has been evaluated in several randomized trials, including the recently concluded T1D Exchange Network trial in adolescents and the REMOVAL trial in adults. Metformin reduces the insulin dose requirement, insulin-induced weight gain, and total and LDL cholesterol, but results in an increased risk of gastrointestinal adverse effects and a minor increase in the risk of hypoglycemia. In addition, metformin has been shown to reduce maximal carotid intima media thickness and therefore may extend cardioprotective benefits in type 1 diabetes. The role of metformin as adjunctive therapy in type 1 diabetes needs to be explored further in outcome trials.
Literature
1.
go back to reference Sherr J, Tsalikian E, Fox L, et al. Dysregulation of alpha-cell function in youth during the first 2 years of T1D: recipricol abnormalities in glucagon responses to mixed meal feedings and hypoglycemia. Diabetes. 2012;61(Supplement 1):A52–3. Sherr J, Tsalikian E, Fox L, et al. Dysregulation of alpha-cell function in youth during the first 2 years of T1D: recipricol abnormalities in glucagon responses to mixed meal feedings and hypoglycemia. Diabetes. 2012;61(Supplement 1):A52–3.
6.
go back to reference Liu LL, Lawrence JM, Davis C, Liese AD, Pettitt DJ, Pihoker C, Dabelea D, Hamman R, Waitzfelder B, Kahn HS. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth study. Pediatr Diabetes. 2010;11(1):4–11.CrossRefPubMed Liu LL, Lawrence JM, Davis C, Liese AD, Pettitt DJ, Pihoker C, Dabelea D, Hamman R, Waitzfelder B, Kahn HS. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth study. Pediatr Diabetes. 2010;11(1):4–11.CrossRefPubMed
7.
go back to reference DuBose SN, Hermann JM, Tamborlane WV, Beck RW, Dost A, DiMeglio LA, Schwab KO, Holl RW, Hofer SE, Maahs DM. Type 1 diabetes exchange clinic network and diabetes prospective follow-up registry. Obesity in youth with type 1 diabetes in Germany, Austria, and the United States. J Pediatr. 2015;167(3):627-32.e1-4. https://doi.org/10.1016/j.jpeds.2015.05.046 (Epub 2015 Jul 8).CrossRefPubMed DuBose SN, Hermann JM, Tamborlane WV, Beck RW, Dost A, DiMeglio LA, Schwab KO, Holl RW, Hofer SE, Maahs DM. Type 1 diabetes exchange clinic network and diabetes prospective follow-up registry. Obesity in youth with type 1 diabetes in Germany, Austria, and the United States. J Pediatr. 2015;167(3):627-32.e1-4. https://​doi.​org/​10.​1016/​j.​jpeds.​2015.​05.​046 (Epub 2015 Jul 8).CrossRefPubMed
8.
go back to reference Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between type I and type II diabetes. Diabetologia. 2001;44(7):914–22.CrossRefPubMed Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between type I and type II diabetes. Diabetologia. 2001;44(7):914–22.CrossRefPubMed
9.
go back to reference Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom HK. Childhood Diabetes in Finlad Study Group. Obesity, increased linear growth and risk of type 1 diabetes in children. Diabetes Care. 2000;23(12):1755–60.CrossRefPubMed Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom HK. Childhood Diabetes in Finlad Study Group. Obesity, increased linear growth and risk of type 1 diabetes in children. Diabetes Care. 2000;23(12):1755–60.CrossRefPubMed
11.
go back to reference Purnell JQ, Zinman B, Brunzell JD. DCCT/EDIC Research Group. The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) Study. Circulation. 2013;127:180–7.CrossRefPubMed Purnell JQ, Zinman B, Brunzell JD. DCCT/EDIC Research Group. The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) Study. Circulation. 2013;127:180–7.CrossRefPubMed
14.
go back to reference Bacha F, Klinepeter Bartz S. Insulin resistance, role of metformin and other non-insulin therapies in pediatric type 1 diabetes. Pediatric Diabetes. 2016;17:545–58.CrossRefPubMed Bacha F, Klinepeter Bartz S. Insulin resistance, role of metformin and other non-insulin therapies in pediatric type 1 diabetes. Pediatric Diabetes. 2016;17:545–58.CrossRefPubMed
15.
go back to reference DeFronzo RA, Hendler R, Simonson D. Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes. 1982;31(9):795–801.CrossRefPubMed DeFronzo RA, Hendler R, Simonson D. Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes. 1982;31(9):795–801.CrossRefPubMed
17.
go back to reference Nadeau KJ, Regensteiner JG, Bauer TA, et al. Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab. 2010;95(2):513–21.CrossRefPubMed Nadeau KJ, Regensteiner JG, Bauer TA, et al. Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab. 2010;95(2):513–21.CrossRefPubMed
18.
go back to reference Van Vliet M, Van der Heyden JC, Diamant M, Van der Rosenstiel IA, Schindhelm RK, Aanstoot HJ, Veeze HJ. Overweight is highly prevalent in children with type 1 diabetes and associates with cardiometabolic risk. J Pediatr. 2010;156(6):923–9.CrossRefPubMed Van Vliet M, Van der Heyden JC, Diamant M, Van der Rosenstiel IA, Schindhelm RK, Aanstoot HJ, Veeze HJ. Overweight is highly prevalent in children with type 1 diabetes and associates with cardiometabolic risk. J Pediatr. 2010;156(6):923–9.CrossRefPubMed
19.
go back to reference Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N, Leese G, Leslie P, McCrimmon RJ, Metcalfe W, et al. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008–2010. JAMA. 2015;313:37–44.CrossRefPubMedPubMedCentral Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N, Leese G, Leslie P, McCrimmon RJ, Metcalfe W, et al. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008–2010. JAMA. 2015;313:37–44.CrossRefPubMedPubMedCentral
21.
go back to reference Orchard TJ, Olson JC, Erbey JR, Williams K, Forrest KY, Smithline Kinder L, Ellis D, Becker DJ. 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;26:1374–9.CrossRefPubMed Orchard TJ, Olson JC, Erbey JR, Williams K, Forrest KY, Smithline Kinder L, Ellis D, Becker DJ. 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;26:1374–9.CrossRefPubMed
22.
go back to reference Schauer IE, Snell-Bergeon JK, Bergman BC, et al. Insulin resistance, defective insulin-mediated fatty acid suppression, and coronary artery calcification in subjects with and without type 1 diabetes: the CACTI study. Diabetes. 2011;60:306–14.CrossRefPubMed Schauer IE, Snell-Bergeon JK, Bergman BC, et al. Insulin resistance, defective insulin-mediated fatty acid suppression, and coronary artery calcification in subjects with and without type 1 diabetes: the CACTI study. Diabetes. 2011;60:306–14.CrossRefPubMed
24.
go back to reference Gin H, Messerchmitt C, Brottier E, Aubertin J. Metformin improved insulin resistance in type I, insulin-dependent, diabetic patients. Metabolism. 1985;34(10):923–5.CrossRefPubMed Gin H, Messerchmitt C, Brottier E, Aubertin J. Metformin improved insulin resistance in type I, insulin-dependent, diabetic patients. Metabolism. 1985;34(10):923–5.CrossRefPubMed
25.
go back to reference Moon RJ, Bascombe LA, Holt RI. The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-being. Diabetes Obes Metab. 2007;9(1):143–5.CrossRefPubMed Moon RJ, Bascombe LA, Holt RI. The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-being. Diabetes Obes Metab. 2007;9(1):143–5.CrossRefPubMed
27.
go back to reference Gómez R, Mokhashi MH, Rao J, Vargas A, Compton T, McCarter R, Chalew SA. Metformin adjunctive therapy with insulin improves glycemic control in patients with type 1 diabetes mellitus: a pilot study. J Pediatr Endocrinol Metab. 2002;15(8):1147–51.CrossRefPubMed Gómez R, Mokhashi MH, Rao J, Vargas A, Compton T, McCarter R, Chalew SA. Metformin adjunctive therapy with insulin improves glycemic control in patients with type 1 diabetes mellitus: a pilot study. J Pediatr Endocrinol Metab. 2002;15(8):1147–51.CrossRefPubMed
28.
go back to reference Khan AS, McLoughney CR, Ahmed AB. The effect of metformin on blood glucose control in overweight patients with type 1 diabetes. Diabet Med. 2006;23(10):1079–84.CrossRefPubMed Khan AS, McLoughney CR, Ahmed AB. The effect of metformin on blood glucose control in overweight patients with type 1 diabetes. Diabet Med. 2006;23(10):1079–84.CrossRefPubMed
29.
go back to reference Pagano G, Tagliaferro V, Carta Q, Caselle MT, Bozzo C, Vitelli F, Trovati M, Cocuzza E. Metformin reduces insulin requirement in type 1 (insulin-dependent) diabetes. Diabetologia. 1983;24(5):351–4.CrossRefPubMed Pagano G, Tagliaferro V, Carta Q, Caselle MT, Bozzo C, Vitelli F, Trovati M, Cocuzza E. Metformin reduces insulin requirement in type 1 (insulin-dependent) diabetes. Diabetologia. 1983;24(5):351–4.CrossRefPubMed
31.
go back to reference Meyer L, Böhme P, Delbachian I, Lehert P, Cugnardey N, Drouin P, Guerci B. The benefits of metformin therapy during continuous subcutaneous insulin infusion treatment of type 1 diabetic patients. Diabetes Care. 2002;25:2153–8.CrossRefPubMed Meyer L, Böhme P, Delbachian I, Lehert P, Cugnardey N, Drouin P, Guerci B. The benefits of metformin therapy during continuous subcutaneous insulin infusion treatment of type 1 diabetic patients. Diabetes Care. 2002;25:2153–8.CrossRefPubMed
32.
go back to reference Lund SS, Tarnow L, Astrup AS, et al. Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control: a randomized study. PLoS ONE. 2008;3(10):e3363.CrossRefPubMedPubMedCentral Lund SS, Tarnow L, Astrup AS, et al. Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control: a randomized study. PLoS ONE. 2008;3(10):e3363.CrossRefPubMedPubMedCentral
33.
go back to reference Pang TT, Narendran P. Addressing insulin resistance in type 1 diabetes. Diabet Med. 2008;25:1015–24.CrossRefPubMed Pang TT, Narendran P. Addressing insulin resistance in type 1 diabetes. Diabet Med. 2008;25:1015–24.CrossRefPubMed
34.
go back to reference Vella S, Buetow L, Royle P, Livingstone S, Colhoun HM, Petrie JR. The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010;53(5):809–20.CrossRefPubMed Vella S, Buetow L, Royle P, Livingstone S, Colhoun HM, Petrie JR. The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010;53(5):809–20.CrossRefPubMed
35.
go back to reference Liu C, Wu D, Zheng X, et al. Efficacy and safety of metformin for patients with type 1 diabetes mellitus: a meta-analysis. Diabetes Technol Ther. 2015;17:142–8.CrossRefPubMed Liu C, Wu D, Zheng X, et al. Efficacy and safety of metformin for patients with type 1 diabetes mellitus: a meta-analysis. Diabetes Technol Ther. 2015;17:142–8.CrossRefPubMed
37.
go back to reference Petrie JR, Chaturvedi N, Ford I, Brouwers MCGJ, Greenlaw N, Tillin T, Hramiak I, Hughes AD, Jenkins AJ, Klein BEK, Klein R, Ooi TC, Rossing P, Stehouwer CDA, Sattar N, Colhoun HM, REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(8):597–609. https://doi.org/10.1016/S2213-8587(17)30194-8 (Epub 2017 Jun 11).CrossRefPubMedPubMedCentral Petrie JR, Chaturvedi N, Ford I, Brouwers MCGJ, Greenlaw N, Tillin T, Hramiak I, Hughes AD, Jenkins AJ, Klein BEK, Klein R, Ooi TC, Rossing P, Stehouwer CDA, Sattar N, Colhoun HM, REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(8):597–609. https://​doi.​org/​10.​1016/​S2213-8587(17)30194-8 (Epub 2017 Jun 11).CrossRefPubMedPubMedCentral
38.
go back to reference Escobar-Morreale HF, Roldan B, Barrio R, Alonso M, Sancho J, de la Calle H, Garcia-Robles R. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2000;85:4182–7.PubMed Escobar-Morreale HF, Roldan B, Barrio R, Alonso M, Sancho J, de la Calle H, Garcia-Robles R. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2000;85:4182–7.PubMed
39.
go back to reference Codner E, Escobar-Morreale HF. Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007;92:1209–16.CrossRefPubMed Codner E, Escobar-Morreale HF. Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007;92:1209–16.CrossRefPubMed
40.
go back to reference Roldan B, Escobar-Morreale HF, Barrio R, de La Calle H, Alonso M, Garcia-Robles R, Sancho J. Identification of the source of androgen excess in hyperandrogenic type 1 diabetic patients. Diabetes Care. 2001;24:1297–9.CrossRefPubMed Roldan B, Escobar-Morreale HF, Barrio R, de La Calle H, Alonso M, Garcia-Robles R, Sancho J. Identification of the source of androgen excess in hyperandrogenic type 1 diabetic patients. Diabetes Care. 2001;24:1297–9.CrossRefPubMed
42.
go back to reference DCCT Research Group. Effect of intensive diabetes treatment on the development and progression of long term complications in adolescents with insulin-dependent diabetes mellitus. Diabetes Control and Complications Trial. J Pediatrics. 1994;125:177–88.CrossRef DCCT Research Group. Effect of intensive diabetes treatment on the development and progression of long term complications in adolescents with insulin-dependent diabetes mellitus. Diabetes Control and Complications Trial. J Pediatrics. 1994;125:177–88.CrossRef
43.
go back to reference Ferguson AW, De La Harpe PL, Farquhar JW. Dimethyldiguanide in the treatment of diabetic children. Lancet. 1961;1:1367–9.CrossRefPubMed Ferguson AW, De La Harpe PL, Farquhar JW. Dimethyldiguanide in the treatment of diabetic children. Lancet. 1961;1:1367–9.CrossRefPubMed
44.
go back to reference Schatz H, Winkler G, Jonatha EM, Pfeiffer EF. Studies on juvenile-type diabetes in children. Assessment of control under treatment with constant and variable doses of insulin with or without addition of biguanides. Diabete Metab. 1975;1:211–20.PubMed Schatz H, Winkler G, Jonatha EM, Pfeiffer EF. Studies on juvenile-type diabetes in children. Assessment of control under treatment with constant and variable doses of insulin with or without addition of biguanides. Diabete Metab. 1975;1:211–20.PubMed
45.
go back to reference Sarnblad S, Kroon M, Aman J. Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised placebo-controlled trial with aspects on insulin sensitivity. Eur J Endocrinol. 2003;149:323–9.CrossRefPubMed Sarnblad S, Kroon M, Aman J. Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised placebo-controlled trial with aspects on insulin sensitivity. Eur J Endocrinol. 2003;149:323–9.CrossRefPubMed
47.
go back to reference Hamilton J, Cummings E, Zdravkovic V, Finegood D, Daneman D. Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance: a randomized controlled trial. Diabetes Care. 2003;26(1):138–43 PMID: 12502670.CrossRefPubMed Hamilton J, Cummings E, Zdravkovic V, Finegood D, Daneman D. Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance: a randomized controlled trial. Diabetes Care. 2003;26(1):138–43 PMID: 12502670.CrossRefPubMed
50.
51.
go back to reference Pandey AK, Gutch M, Mittal M, Kumar S, Razi SM. Can metformin be used in type 1 diabetes with insulin resistance: experience from tertiary care health center. J Assoc Physicians India. 2016;64(1):91. Pandey AK, Gutch M, Mittal M, Kumar S, Razi SM. Can metformin be used in type 1 diabetes with insulin resistance: experience from tertiary care health center. J Assoc Physicians India. 2016;64(1):91.
53.
go back to reference Konrad K, Datz N, Engelsberger I, Gurlich-Henn J, Hoertenhuber T, Knauth B, Meissner T, Wiegand S, Woelfle J, Holl RW. German/Austrian DPV Initiative. Current use of metformin in addition to insulin in pediatric patients with type 1 diabetes mellitus: an analysis based on a large diabetes registry in Germany and Austria. Pediatr Diabetes. 2015;16(7):529–37. https://doi.org/10.1111/pedi.12203 Epub 2014 Aug 18.CrossRefPubMed Konrad K, Datz N, Engelsberger I, Gurlich-Henn J, Hoertenhuber T, Knauth B, Meissner T, Wiegand S, Woelfle J, Holl RW. German/Austrian DPV Initiative. Current use of metformin in addition to insulin in pediatric patients with type 1 diabetes mellitus: an analysis based on a large diabetes registry in Germany and Austria. Pediatr Diabetes. 2015;16(7):529–37. https://​doi.​org/​10.​1111/​pedi.​12203 Epub 2014 Aug 18.CrossRefPubMed
55.
go back to reference Burchardt P, Zawada A, Tabaczewski P, Naskręt D, Kaczmarek J, Marcinkaniec J, Wierusz-Wysocka B, Wysocki H. Metformin added to intensive insulin therapy reduces plasma levels of glycated but not oxidized low–density lipoprotein in young patients with type 1 diabetes and obesity in comparison with insulin alone: a pilot study. Pol Arch Med Wewn. 2013;123(10):526–32 Epub 2013 Aug 8.PubMed Burchardt P, Zawada A, Tabaczewski P, Naskręt D, Kaczmarek J, Marcinkaniec J, Wierusz-Wysocka B, Wysocki H. Metformin added to intensive insulin therapy reduces plasma levels of glycated but not oxidized low–density lipoprotein in young patients with type 1 diabetes and obesity in comparison with insulin alone: a pilot study. Pol Arch Med Wewn. 2013;123(10):526–32 Epub 2013 Aug 8.PubMed
56.
go back to reference Lund SS, Tarnow L, Astrup AS, et al. Effect of adjunct metformin treatment on levels of plasma lipids in patients with type 1 diabetes. Diabetes Obes Metab. 2009;11(10):966–77.CrossRefPubMed Lund SS, Tarnow L, Astrup AS, et al. Effect of adjunct metformin treatment on levels of plasma lipids in patients with type 1 diabetes. Diabetes Obes Metab. 2009;11(10):966–77.CrossRefPubMed
57.
go back to reference Pitocco D, Zaccardi F, Tarzia P, et al. Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study. Diabetes Obes Metab. 2013;15:427–31.CrossRefPubMed Pitocco D, Zaccardi F, Tarzia P, et al. Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study. Diabetes Obes Metab. 2013;15:427–31.CrossRefPubMed
59.
go back to reference Matsumoto K, Gera Y, Abe Y, Tominanga T, Yeki Y, Miyake S. Metformin attenuates progression of carotid arterial wall thickness in patients with type 2 diabetes. Diabetes Res Clin Pract. 2004;64:225–8.CrossRefPubMed Matsumoto K, Gera Y, Abe Y, Tominanga T, Yeki Y, Miyake S. Metformin attenuates progression of carotid arterial wall thickness in patients with type 2 diabetes. Diabetes Res Clin Pract. 2004;64:225–8.CrossRefPubMed
60.
go back to reference Burchardt P, Zawada A, Kaczmarek J, et al. Association between adjunctive metformin therapy in young type 1 diabetes patients with excess body fat and reduction of carotid intima-media thickness. Pol Arch Med Wewn. 2016;126(7–8):514–20. https://doi.org/10.20452/pamw.3527.PubMed Burchardt P, Zawada A, Kaczmarek J, et al. Association between adjunctive metformin therapy in young type 1 diabetes patients with excess body fat and reduction of carotid intima-media thickness. Pol Arch Med Wewn. 2016;126(7–8):514–20. https://​doi.​org/​10.​20452/​pamw.​3527.PubMed
61.
go back to reference Miller KM, Foster NC, Beck RW, et al. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes Care. 2015;38:971–8.CrossRefPubMed Miller KM, Foster NC, Beck RW, et al. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes Care. 2015;38:971–8.CrossRefPubMed
62.
go back to reference Morris AD, Boyle DI, MacAlpine R, et al. The diabetes audit and research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration. BMJ. 1997;315:524–8.PubMed Morris AD, Boyle DI, MacAlpine R, et al. The diabetes audit and research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration. BMJ. 1997;315:524–8.PubMed
63.
go back to reference American Diabetes Association (2017) Standards ofmedical care in diabetes. Diabetes Care 2017; 40 (Suppl 1):S1–S135. American Diabetes Association (2017) Standards ofmedical care in diabetes. Diabetes Care 2017; 40 (Suppl 1):S1–S135.
Metadata
Title
A Review of Insulin Resistance in Type 1 Diabetes: Is There a Place for Adjunctive Metformin?
Authors
Gagan Priya
Sanjay Kalra
Publication date
01-02-2018
Publisher
Springer Healthcare
Published in
Diabetes Therapy / Issue 1/2018
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-017-0333-9

Other articles of this Issue 1/2018

Diabetes Therapy 1/2018 Go to the issue