Diabetes-related Complications: US Trends in the Last 20 Years

Cardiology Review® Online, August 2014, Volume 30, Issue 4

The incidence of type 2 diabetes mellitus tripled in the last 20 years. What has that meant for rates of complications?

Niki Katsiki, MSc, PhD, MD, FRSPH


Gregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990—2010. New Eng J Med. 2014;370:1514-1523.

Type 2 diabetes mellitus (T2DM) has become a pandemic.1 However, T2DM care has improved over the last decades in terms of treatment of risk factors (eg, high glucose, lipids, and blood pressure [BP]), health-system delivery, social support, and patient education.2 These approaches can reduce the risk of T2DM-related complications, therefore increasing both quality of life and survival. In the present study, Gregg et al3 compared the rates of T2DM-related acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), lower-extremity amputation, and death from hyperglycemic crisis in the US population between 1990 and 2010. Rates of these complications were also examined with regard to the overall population.

Study Design

Gregg et al3 assessed data from US surveys [the National Health Interview Survey and the National Hospital Discharge Survey] and registries [the US Renal Data System and the National Vital Statistics System] to identify cases of T2DM-related morbidity (ie, AMI, stroke, lower-extremity amputation, and ESRD) and mortality (defined as death from hyperosmolar hyperglycemic states and diabetic ketoacidosis) between 1990 and 2010. Incident rates were calculated both for the US diabetic population (≥20 years old) and the overall US population of the same age. Sensitivity analyses were performed to avoid bias of changes in diagnostic procedures. Rates were presented as events per 10,000 person-years in 4 age groups: 20 to 44, 45 to 64, 65 to 74, and ≥75 years.

T2DM prevalence in US adults tripled between 1990 and 2010 (6.5 vs 20.7 million, respectively); the overall adult population increased by 27%. The rates of all the studied diabetic complications were significantly decreased during these decades; the absolute decline was greater for AMI (95.6 fewer cases per 10,000 persons; 95% confidence interval [CI], 76.6 to 114.6), followed by stroke, lower-extremity amputation, ESRD, and death from hyperglycemic crisis (58.9, 30.0, 7.9, and 2.7 fewer cases per 10,000 persons, respectively; 95% CI, 41.6 to 76.2, 17.4 to 42.6, 5.5 to 10.2, and 2.4 to 3.0, respectively). These reductions were first observed in 1995 and remained consistent afterward. With regard to the absolute annual numbers of cases, irrespective of population size, only the number of cases of AMI and death from hyperglycemic crisis were reduced (by 4379 cases and 529 deaths, respectively), whereas the number of cases of stroke, ESRD, and amputation were increased (by 59,703, 32,434, and 22,703 cases, respectively).

Relative declines were also observed in the rates of all T2DM-related complications3: the greatest reduction was seen for AMI (—67.8%; 95% CI, –76.2 to –59.3), followed by death from hyperglycemic crisis, stroke, amputation, and ESRD (–64.4, –52.7, –51.4, and –28.3%, respectively; 95% CI, –68.0 to –60.9, –64.4 to –40.9, –68.2 to –34.5, and –34.6 to –21.6, respectively). With regard to age, both absolute and relative declines were greater in older persons (ie, ≥75 years) with the exception of ESRD, where rates were reduced only in younger adults (ie, <65 years). Death from hyperglycemic crisis was more frequent in younger individuals; amputation rates were similar between younger and older adults, whereas AMI and stroke age differences were narrowed.

However, when data were compared between 2000 (instead of 1990) and 2010, decreases were observed in all age groups. No significant gender or race discrepancies were observed with the exception of AMI, in which case gender differences were minimized.

For the overall US adult population, the relative decline was greater in the rates for death from hyperglycemic crisis, followed by AMI (—42.0% and –32.3%, respectively), whereas rates for stroke and amputation remained unchanged.3 In contrast, ESRD prevalence increased by 90.9%. In adults without T2DM, AMI rates were decreased to a smaller extent than in patients with diabetes (—31.2% vs –67.8%, respectively), stroke and amputation incidence did not change significantly (–5.5% and –12.9%, respectively) and ESRD prevalence increased (by 65%). Therefore, the relative risk of T2DM-related complications was substantially reduced for AMI (from 3.8 [95% CI, 3.3 to 4.2] to 1.8 [95% CI, 1.3 to 2.3]), stroke (from 3.1 [95% CI, 2.7 to 3.5] to 1.5 [95% CI, 1.1 to 2.0]), amputation (from 18.8 [95% CI, 15.1 to 22.6] to 10.5 [95% CI, 6.0 to 15.0]), and ESRD (from 13.7 [95% CI, 12.6 to 14.9] to 6.1 [95% CI, 5.7 to 6.3]).


Improvement in complication rates, but rising number of cases

In their discussion, Gregg et al3 mentioned that the observed reductions in T2DM-related complications may be attributed to improvements in primary and acute care settings, health-system performance, patient education in self-management, and health-promoting society policies. Such approaches can lead to better treatment of risk factors (including glucose, A1C, lipids, BP, and smoking), thus preventing diabetes-related complications. Furthermore, early detection of such complications, wound healing, the performance of revascularization procedures, and improvements in managing acute hyperglycemic abnormalities in hospitals may have also played a role in decreasing the rates of T2DM-related morbidity and mortality. According to the authors, both absolute and relative reductions were greater for AMI, most likely due to the improvements and more frequent use of coronary revascularization procedures in the last decades; the rates for ESRD declined at a smaller extent in US patients with T2DM (and were even increased in the overall population and in nondiabetic adults), possibly due to an increased percentage of non-Hispanic blacks in the diabetic US population over the years, a raised life expectancy that may increase the risk of developing ESRD, and delayed initiation of dialysis.3

In the present analysis3 there are no data with regard to circulating biomarkers (ie, glucose, A1C, and lipids) as well as BP. Therefore, the effect of achieving treatment goals on the incidence of T2DM-related complications cannot be evaluated. Current evidence shows that glucose, lipid, and BP targets are not sufficiently reached in clinical practice in the United States4,5 and Europe.6 The improvement of clinical implementation of current guidelines may increase the proportion of patients achieving treatment goals, thus reducing or even preventing the development of T2DM and T2DM-related complications.

Gregg et al3 reported several limitations of their analysis, including the lack of data on other diabetic complications such as retinopathy, nephropathy, neuropathy, and peripheral artery disease as well as hypoglycemia. The rates of obesity, metabolic syndrome (MetS), and non-alcoholic fatty liver disease (NAFLD) were also not evaluated. In this context, obesity, MetS, and NAFLD have been reported to increase the risk for T2DM and T2DM-related complications.7-10 Prevention of these metabolic disorders or at least earlier diagnosis (even in childhood) and effective treatment may prevent or delay the onset of T2DM. Therefore, better treatments may be available at the time a patient develops T2DM. Also, as T2DM-related complications are time dependent, the later the onset of T2DM, the better.

Gregg et al3 do not comment on treatment. The use of drugs targeting cardiovascular risk and treating T2DM has substantially changed over the last 2 decades. In this context, statins are more frequently prescribed over the time span studied, and they have been associated with significant reductions in T2DM-related vascular complications, although a link with new-onset diabetes (NOD) has been reported.11,12 Antihypertensive drugs may differentially affect weight, glucose, and lipid metabolism; renin-angiotensin system inhibitors represent the first-line therapeutic option to treat hypertension in patients with T2DM due to their beneficial effects in terms of T2DM-related vascular morbidity and mortality and their lack of metabolic adverse events.13 Incretin-based therapies have substantially altered the management of patients with diabetes. Apart from glucose control, glucagon-like peptide—1 (GLP-1) receptor agonists have been shown to beneficially affect weight, lipids, and BP, and may also exert direct cardioprotective effects.14 Similar metabolic and cardiovascular benefits have been reported for dipeptidyl peptidase—4 (DPP-4) inhibitors.15 Sodium glucose cotransporter 2 (SGLT2) inhibitors may also improve weight, BP, and lipid levels, although data are still limited.16 The use of antiplatelet agents increased during the last decades. With regard to vascular complications, timely antiplatelet treatment may improve T2DM-related morbidity and mortality.17

Multifactorial intervention is of great importance in reducing the risk of T2DM and T2DM-related vascular morbidity.18 In this context, a post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study showed that after targeting multiple risk factors by lifestyle measures and drug therapy (including a statin), the 3.5-year incidences of NOD and cardiovascular events in MetS patients were similar to the general population.19 Multifactorial treatment (including a statin) is also beneficial in both the prevention and management of MetS and NAFLD.20,21

In conclusion, T2DM-related morbidity and mortality has been substantially reduced during the last 2 decades. However, there is still a need for further improvements in prevention, early diagnosis, and effective treatment of T2DM and T2DM-related complications, especially in the light of the rapidly increasing prevalence of obesity and T2DM worldwide.


  1. Fava S. Glycaemic control: a balancing act or a different approach? Curr Diabetes Rev. 2014;10:124-130.
  2. Erlich DR, Slawson DC, Shaughnessy A. Diabetes update: population management. FP Essent. 2013;408:25-33.
  3. Gregg EW, Li Y, Wang J, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014;370:1514-1523.
  4. Chopra I, Kamal KM, Candrilli SD. Variations in blood pressure and lipid goal attainment in primary care. Curr Med Res Opin. 2013;29:1115-1125.
  5. Schroeder EB, Hanratty R, Beaty BL, Bayliss EA, Havranek EP, Steiner JF. Simultaneous control of diabetes mellitus, hypertension, and hyperlipidemia in 2 health systems. Circ Cardiovasc Qual Outcomes. 2012;5:645-653.
  6. European Society of Cardiology. EUROASPIRE IV reveals success and challenges in secondary prevention of CVD across Europe. September 3, 2013. http://www.escardio.org/about/press/press-releases/esc13-amsterdam/Pages/euroaspire-iv-success-challenges-secondary-prevention-CVD-europe.aspx
  7. Scheen AJ, Van Gaal LF. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes [published online February 19, 2014]. Lancet Diabetes Endocrinol. 2014.
  8. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Metabolic syndrome and non-cardiac vascular diseases: an update from human studies [published online December 5, 2013]. Curr Pharm Des. 2013.
  9. Lioudaki E, Ganotakis ES, Mikhailidis DP. Liver enzymes: potential cardiovascular risk markers? Curr Pharm Des. 2011;17:3632-3643.
  10. Targher G, Byrne CD. Clinical Review: Nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J Clin Endocrinol Metab. 2013;98:483-495.
  11. Athyros VG, Mikhailidis DP. Pharmacotherapy: statins and new-onset diabetes mellitus. A matter for debate. Nat Rev Endocrinol. 2012;8:133-134.
  12. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. The role of statins in the treatment of type 2 diabetes mellitus: an update. Curr Pharm Des. 2014;20:3665-3674.
  13. Patel BM, Mehta AA. Choice of anti-hypertensive agents in diabetic subjects. Diab Vasc Dis Res. 2013;10:385-396.
  14. Lorber D. GLP-1 receptor agonists: effects on cardiovascular risk reduction. Cardiovasc Ther. 2013;31:238-249.
  15. Balakumar P, Dhanaraj SA. Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials. Cell Signal. 2013;25:1799-1803.
  16. Fujita Y, Inagaki N. Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: Clinical data and mechanism of action. J Diabetes Investig. 2014;5:265-275.
  17. Beckman JA, Paneni F, Cosentino F, Creager MA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Eur Heart J. 2013;34:2444-2452.
  18. Lorber D. Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes. 2014;7:169-183.
  19. Athyros VG, Elisaf MS, Alexandrides T, et al; Assessing the Treatment Effect in Metabolic Syndrome Without Perceptible Diabetes (ATTEMPT) Collaborative Group. Long-term impact of multifactorial treatment on new-onset diabetes and related cardiovascular events in metabolic syndrome: a post hoc ATTEMPT analysis. Angiology. 2012;63:358-366.
  20. Polyzos SA, Kountouras J, Zavos C, Deretzi G. Nonalcoholic fatty liver disease: multimodal treatment options for a pathogenetically multiple-hit disease. J Clin Gastroenterol. 2012;46:272-284.
  21. Wang Y, Yu Q, Chen Y, Cao F. Pathophysiology and therapeutics of cardiovascular disease in metabolic syndrome. Curr Pharm Des. 2013;19:4799-4805.

About the Author

Niki Katsiki, MSC, PhD, MD, FRSPH, is a specialist in internal medicine and a researcher at the Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. Her PhD is based on obesity-related peptides in diabetic patients. Dr Katsiki’s clinical and research interests involve cardiovascular disease prevention and treatment. She has participated in obesity, lipid, diabetes, peripheral artery disease, and smoking cessation outpatient clinics with a special focus on dyslipidemias. Dr Katsiki was an honorary clinical research fellow at the Department of Clinical Biochemistry (Academic Head, DP Mikhailidis), Royal Free Hospital campus, University College London Medical School, University College London (UCL), UK. She is also a SCOPE member of the International Association for the Study of Obesity. Dr Katsiki serves as a reviewer for several cardiovascular journals and is the editorial manager of Angiology and section editor of Archives of Medical Science. She was assisted in the writing of this article by Dimitri P. Mikhailidis, BSc, MSc, MD, FRSPH, FCP, FFPM, FRCP, FRCPath, academic head of the Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), and Department of Surgery, Royal Free Campus, University College London Medical School, UCL, London, UK. He is editor-in-chief of several journals including Current Medical Research and Opinion, Current Vascular Pharmacology, and Expert Opinion on Pharmacotherapy.