Type 2 diabetes prevalence is increasing worldwide, driven by increasing prevalence of obesity and overweight and compounded by population growth and aging.[4]NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016 Apr 6;387(10027):1513-30.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00618-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27061677?tool=bestpractice.com
[5]Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2014 Mar 22;383(9922):1068-83.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226760
http://www.ncbi.nlm.nih.gov/pubmed/24315620?tool=bestpractice.com
Between 2000 and 2021, global age-standardized prevalence increased from 4.6% to 10.5%.[6]International Diabetes Federation. IDF diabetes atlas: 10th edition. 2021 [internet publication].
https://diabetesatlas.org/atlas/tenth-edition
However, while the overall burden of type 2 diabetes is increasing, trends in the incidence rate plateaued from the mid-2000s and now appear to be decreasing.[7]Magliano DJ, Islam RM, Barr ELM, et al. Trends in incidence of total or type 2 diabetes: systematic review. BMJ. 2019 Sep 11;366:l5003.
https://www.bmj.com/content/366/bmj.l5003.long
http://www.ncbi.nlm.nih.gov/pubmed/31511236?tool=bestpractice.com
Data from the US National Health Interview Survey documented that the incidence of age-adjusted, diagnosed diabetes decreased from 2007 to 2017, from 7.8 to 6.0 per 1000 adults.[8]Benoit SR, Hora I, Albright AL, et al. New directions in incidence and prevalence of diagnosed diabetes in the USA. BMJ Open Diabetes Res Care. 2019 May 28;7(1):e000657.
https://drc.bmj.com/content/7/1/e000657
http://www.ncbi.nlm.nih.gov/pubmed/31245008?tool=bestpractice.com
This may be in part due to increased awareness, education, and risk factor modification.[7]Magliano DJ, Islam RM, Barr ELM, et al. Trends in incidence of total or type 2 diabetes: systematic review. BMJ. 2019 Sep 11;366:l5003.
https://www.bmj.com/content/366/bmj.l5003.long
http://www.ncbi.nlm.nih.gov/pubmed/31511236?tool=bestpractice.com
Lifetime risk of diabetes is now 40% for both men and women in the overall US population, and is 50% in the US African-American population.[9]Gregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014 Apr 17;370(16):1514-23.
https://www.nejm.org/doi/full/10.1056/NEJMoa1310799
http://www.ncbi.nlm.nih.gov/pubmed/24738668?tool=bestpractice.com
Evidence also shows an increased prevalence of type 2 diabetes in the Asian-American population (when compared with non-Hispanic white adults), and based on limited data available, this appears to be true to varying degrees across all Asian-American subgroups.[10]Kwan TW, Wong SS, Hong Y, et al. Epidemiology of diabetes and atherosclerotic cardiovascular disease among Asian American adults: implications, management, and future directions: a scientific statement from the American Heart Association. Circulation. 2023 Jul 4;148(1):74-94.
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001145
http://www.ncbi.nlm.nih.gov/pubmed/37154053?tool=bestpractice.com
Type 2 diabetes accounts for approximately 90% of all diabetes cases and has a prevalence of 8.5% in the US.[11]Xu G, Liu B, Sun Y, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. BMJ. 2018 Sep 4;362:k1497.
https://www.bmj.com/content/362/bmj.k1497.long
http://www.ncbi.nlm.nih.gov/pubmed/30181166?tool=bestpractice.com
Clinical onset is usually preceded by many years of insulin resistance and hyperinsulinemia before elevated glucose levels are detectable.[1]Meigs JB, Muller DC, Nathan DM, et al. The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging. Diabetes. 2003 Jun;52(6):1475-84.
https://diabetes.diabetesjournals.org/content/52/6/1475.full
http://www.ncbi.nlm.nih.gov/pubmed/12765960?tool=bestpractice.com
Reflecting the insidious onset of the condition, high rates of undiagnosed type 2 diabetes have been reported. In the US, 29.4 million adults were living with diabetes in 2021; of those, 8.7 million (28%) were undiagnosed, corresponding to 3.4% of all adults.[12]The Lancet Diabetes Endocrinology. Undiagnosed type 2 diabetes: an invisible risk factor. Lancet Diabetes Endocrinol. 2024 Apr;12(4):215.
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00072-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38460527?tool=bestpractice.com
By the time of clinical onset of diabetes, there has already been significant loss of beta cell mass and function.[13]Chen C, Cohrs CM, Stertmann J, et al. Human beta cell mass and function in diabetes: recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab. 2017 Sep;6(9):943-57.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605733
http://www.ncbi.nlm.nih.gov/pubmed/28951820?tool=bestpractice.com
Patients with type 2 diabetes have a very high risk of concurrent hypertension (80% to 90%), lipid disorders (70% to 80%), and overweight or obesity (60% to 70%).[14]Preis SR, Pencina MJ, Hwang SJ, et al. Trends in cardiovascular disease risk factors in individuals with and without diabetes mellitus in the Framingham Heart Study. Circulation. 2009 Jul 6;120(3):212-20.
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.108.846519
http://www.ncbi.nlm.nih.gov/pubmed/19581493?tool=bestpractice.com
According to one systematic review, approximately 32% of patients with type 2 diabetes globally are affected by cardiovascular disease.[15]Einarson TR, Acs A, Ludwig C, et al. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018 Jun 8;17(1):83.
https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0728-6
http://www.ncbi.nlm.nih.gov/pubmed/29884191?tool=bestpractice.com
On average, adults with type 2 diabetes are up to twice as likely to die of stroke or myocardial infarction compared with those without diabetes.[16]Hansen MB, Jensen ML, Carstensen B. Causes of death among diabetic patients in Denmark. Diabetologia. 2012 Feb;55(2):294-302.
http://www.ncbi.nlm.nih.gov/pubmed/22127411?tool=bestpractice.com
[17]Tancredi M, Rosengren A, Svensson AM, et al. Excess mortality among persons with type 2 diabetes. N Engl J Med. 2015 Oct 29;373(18):1720-32.
https://www.nejm.org/doi/full/10.1056/NEJMoa1504347
http://www.ncbi.nlm.nih.gov/pubmed/26510021?tool=bestpractice.com
[18]Desai JR, Vazquez-Benitez G, Xu Z, et al. Who must we target now to minimize future cardiovascular events and total mortality? Lessons from the surveillance, prevention and management of diabetes mellitus (SUPREME-DM) cohort study. Circ Cardiovasc Qual Outcomes. 2015 Sep;8(5):508-16.
https://www.ahajournals.org/doi/full/10.1161/circoutcomes.115.001717
http://www.ncbi.nlm.nih.gov/pubmed/26307132?tool=bestpractice.com
While evidence suggests a link between suboptimal glycemic control and increased risk of cardiovascular (CV) events, the results from randomized controlled trials investigating the impact of optimizing glycemic management on CV risk in patients with type 2 diabetes have produced varied and sometimes seemingly contradictory findings.[19]Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53.
http://www.ncbi.nlm.nih.gov/pubmed/9742976?tool=bestpractice.com
[20]Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89.
https://www.nejm.org/doi/10.1056/NEJMoa0806470
http://www.ncbi.nlm.nih.gov/pubmed/18784090?tool=bestpractice.com
[21]Patel A, MacMahon S, et al; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 6;358(24):2560-72.
https://www.nejm.org/doi/full/10.1056/NEJMoa0802987
http://www.ncbi.nlm.nih.gov/pubmed/18539916?tool=bestpractice.com
[22]Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009 Jan 8;360(2):129-39.
http://www.nejm.org/doi/full/10.1056/NEJMoa0808431#t=article
http://www.ncbi.nlm.nih.gov/pubmed/19092145?tool=bestpractice.com
[23]Gerstein HC, Miller ME, Byington RP, et al; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59.
https://www.nejm.org/doi/full/10.1056/NEJMoa0802743
http://www.ncbi.nlm.nih.gov/pubmed/18539917?tool=bestpractice.com
However, data indicate that a multifactorial risk factor intervention involving optimal management of glucose, blood pressure, lipids, smoking, and weight is associated with a risk of major CV events comparable to that of age- and sex-matched individuals without diabetes.[24]Rawshani A, Rawshani A, Franzén S, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018 Aug 16;379(7):633-44.
https://www.nejm.org/doi/10.1056/NEJMoa1800256
http://www.ncbi.nlm.nih.gov/pubmed/30110583?tool=bestpractice.com
[25]Berkelmans GF, Gudbjörnsdottir S, Visseren FL, et al. Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with type 2 diabetes mellitus. Eur Heart J. 2019 Sep 7;40(34):2899-906.
http://www.ncbi.nlm.nih.gov/pubmed/30629157?tool=bestpractice.com
[26]Gaede P, Lund-Andersen H, Parving HH, et al. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008 Feb 7;358(6):580-91.
https://www.nejm.org/doi/10.1056/NEJMoa0706245
http://www.ncbi.nlm.nih.gov/pubmed/18256393?tool=bestpractice.com
[27]Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003 Jan 30;348(5):383-93.
https://www.nejm.org/doi/full/10.1056/NEJMoa021778
http://www.ncbi.nlm.nih.gov/pubmed/12556541?tool=bestpractice.com
The epidemiology of complications of type 2 diabetes is changing.[28]Harding JL, Pavkov ME, Magliano DJ, et al. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019 Jan 31;62(1):3-16.
https://link.springer.com/article/10.1007/s00125-018-4711-2
http://www.ncbi.nlm.nih.gov/pubmed/30171279?tool=bestpractice.com
The emergence of newer glucose-lowering agents such as sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists has contributed to this, as these agents have demonstrated significant CV benefits, frequently independent of intensive glucose lowering.[29]Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28.
https://www.nejm.org/doi/10.1056/NEJMoa1504720
http://www.ncbi.nlm.nih.gov/pubmed/26378978?tool=bestpractice.com
[30]Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee on behalf of the LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22.
https://www.nejm.org/doi/full/10.1056/NEJMoa1603827
http://www.ncbi.nlm.nih.gov/pubmed/27295427?tool=bestpractice.com
[31]Marso SP, Bain SC, Consoli A, et al; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-44.
https://www.nejm.org/doi/full/10.1056/NEJMoa1607141
http://www.ncbi.nlm.nih.gov/pubmed/27633186?tool=bestpractice.com
Rates of macrovascular complications (e.g., myocardial infarction, lower extremity amputation) and hyperglycemic death have declined in high-income countries due to improvements in multiple-risk factor management and diabetes care.[28]Harding JL, Pavkov ME, Magliano DJ, et al. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019 Jan 31;62(1):3-16.
https://link.springer.com/article/10.1007/s00125-018-4711-2
http://www.ncbi.nlm.nih.gov/pubmed/30171279?tool=bestpractice.com
[32]Chen L, Islam RM, Wang J, et al. A systematic review of trends in all-cause mortality among people with diabetes. Diabetologia. 2020 Sep;63(9):1718-35.
https://link.springer.com/article/10.1007%2Fs00125-020-05199-0
http://www.ncbi.nlm.nih.gov/pubmed/32632526?tool=bestpractice.com
[33]Gregg EW, Sattar N, Ali MK. The changing face of diabetes complications. Lancet Diabetes Endocrinol. 2016 Jun;4(6):537-47.
http://www.ncbi.nlm.nih.gov/pubmed/27156051?tool=bestpractice.com
Data on rates of microvascular complications (e.g., diabetic kidney disease, diabetic retinopathy, neuropathy) are scarce and trends are less conclusive.[28]Harding JL, Pavkov ME, Magliano DJ, et al. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019 Jan 31;62(1):3-16.
https://link.springer.com/article/10.1007/s00125-018-4711-2
http://www.ncbi.nlm.nih.gov/pubmed/30171279?tool=bestpractice.com
When diabetes is diagnosed at age 40 years, men lose an average of 5.8 years of life, and women lose an average of 6.8 years of life, highlighting the importance of primary prevention of the disease.[34]Gregg EW, Zhuo X, Cheng YJ, et al. Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985-2011: a modelling study. Lancet Diabetes Endocrinol. 2014 Nov;2(11):867-74.
http://www.ncbi.nlm.nih.gov/pubmed/25128274?tool=bestpractice.com
Young-onset (<40 years) type 2 diabetes is associated with worse metabolic control and an increased risk of chronic complications and all-cause mortality.[32]Chen L, Islam RM, Wang J, et al. A systematic review of trends in all-cause mortality among people with diabetes. Diabetologia. 2020 Sep;63(9):1718-35.
https://link.springer.com/article/10.1007%2Fs00125-020-05199-0
http://www.ncbi.nlm.nih.gov/pubmed/32632526?tool=bestpractice.com
However, onset of diabetes at older ages has much less effect on life expectancy if acceptable glucose, blood pressure, and lipid management can be achieved and maintained.