Classical type 2 diabetes is characterized by chronic hyperglycemia due to insulin resistance, reduced insulin secretion, and increased hepatic glucose production. The molecular reasons for these defects are unknown. Type 2 diabetes has a genetic component with more than 75 genes being identified as increasing the risk of type 2 diabetes; current research is exploring the contribution of specific genes.
Type 2 diabetes accounts for about 90% to 95% of all diabetes cases (Table 19). 3 In addition, the prevalence of type 2 diabetes in US children and adolescents under the age of 20 years has been estimated at 0.046%.1
|Diabetes (all types)||Type 2 diabetes (estimated)|
|Total||9.3% (29.1 million)||8.4 – 8.8% (26.19 – 27.64 million)|
|diagnosed||72.2% (21.0 million)||64.9 – 68.6 (18.9 – 19.95 million)|
|undiagnosed||27.8% (8.1 million)||25.0 – 26.4 (7.3 – 7.7 million)|
Source: Centers for Disease Control and Prevention. 20143
A comparative analysis of NHANES data between 1988-1994 and 2005-2010 showed a 51.2% (14.9 vs. 29.9 million) increase in the prevalence of type 2 diabetes across all ages of the US population.48 In addition, data from the SEARCH for Diabetes in Youth study reported an incidence of 3,600 cases per year between 2002-2005 (0.4/100,000 cases at age <10 years, and 8.5/100,000 cases at age ≥ 10 years), and a prevalence of 30.5% between 2001-2009.1
The prevalence of type 2 diabetes is markedly higher in Native American/Alaska Native, African American, and Hispanic adults than their non-Hispanic white or Asian counterparts (Table 20). A similar trend holds for US adolescents.
|Adults, age 19 years and older||Adolescents, age 10-19 years|
|Native Americans/Alaska Natives||15.9%||0.120%|
Source: Adults, Centers for Disease Control and Prevention. 20143; adolescents, Dabalea et al. 20141
Compared to the national rate, some geographic areas appear to have higher rates than others. For example, a study of 510 schools representing 252,896 schoolchildren in Philadelphia, Pennsylvania found that the prevalence of type 2 diabetes was higher among African American children (2.8%) compared with white (0.3%) and Hispanic children (0.5%). Mean age at diagnoses of type 2 diabetes was 11.9 years. 40
Treated by conventional glycemic control, young adults with newly diagnosed type 2 diabetes lose about 15 years of their remaining life expectancy compared with a young adult without diabetes. Intensive treatment led to lower lifetime cumulative incidence and lower mortality from microvascular complications such as end-stage renal disease, 19.4% versus 25.2%.49
While the parallel rise in incidence of type 2 diabetes with the prevalence of obesity is clear, the relationship between BMI and all-cause mortality in type 2 diabetes patients is more difficult to pinpoint.
In a retrospective study of 106,640 Scottish patients, there were 9,631 deaths. Patients categorized as normal weight (BMI 20 to <25) or obese (BMI ≥35) with type 2 diabetes within a year of diagnosis of type 2 diabetes exhibited variably higher mortality outcomes compared with the overweight group, confirming a U-shaped association of BMI with mortality. The U-shaped relationship persisted for vascular disease. There is a possible explanation for this “obesity paradox”: People who have a lower body mass at the time of diagnosis may have a different, potentially more aggressive, pathophysiology from those who develop it when obese: an increased sensitivity to visceral fat accumulation, a stronger genetic tendency to insulin resistance, or early pancreatic islet failure, all factors potentially giving a different disease phenotype associated with higher mortality.50 However, this concept is controversial, and the findings could well be due to methodology.
A study of 11,427 health professionals diagnosed with type 2 diabetes who were free of cardiovascular disease and cancer at time of diagnosis found different results. There were 3083 deaths over 15.8 years of follow-up. The authors observed a J-shaped association between BMI and mortality among all participants and among those who had ever smoked and a direct linear relationship among those who had never smoked. They found no evidence of lower mortality among patients with diabetes who were overweight or obese at diagnosis, as compared with their normal-weight counterparts, or of an obesity paradox.51
Although a number of treatment options are available for the treatment of type 2 diabetes, only 53% of patients with diabetes achieve A1C targets of < 7.0%.52 Medication adherence is one of the challenges that patients face in achieving glycemic control. Analysis of retrospective studies using large bases found that adherence to oral hypoglycemic agents ranged from 36-93%; a similar rate was estimated by observational (noncomparative) studies, which found 79-85% adherence during 6-36 months of observation.53 These data also indicated that the less frequently a patient had to take their medication, the higher the adherence rate: for example, once-daily regimens had higher adherence than twice-daily, and monotherapy regimens had higher adherence than polytherapy.53
Metformin is considered to be the first-line therapy for newly diagnosed type 2 diabetes patients. A number of additional pharmacotherapies are available to those adult patients that are inadequately treated by metformin alone. Over the past decade, four new oral medication classes and 10 injectable agents and insulin products have been approved by the FDA for type 2 diabetes treatment.54,55 Overall, the number of adult patients using antidiabetic medications increased by 42.9% between 2003-2012.56 A total of 154.5 million prescriptions were dispensed for antidiabetic drugs in 2012, of which 78.4% were for noninsulin medications.56 Trends for specific drug classes are provided in Table 21; please note that SGLT-2 inhibitors were still new to the market at the time of this study and not included in the overall analysis.
|Medication Type||Medication Class||Number of Prescriptions in 2012 (in millions)|
|Biguanides (e.g., metformin)||60.4|
|Insulins and insulin analogs||All||33.4|
Source: Hampp et al. 201456
Weighted data from NHANES indicated a 7.4% increase in A1C levels among patients with diabetes from NHANES 2007-2008 to NHANES 2009-2010.57 40% to 60% of middle-aged US adults with type 2 diabetes have poor glycemic control, and type 2 diabetes patients age 51-64 years had worse glycemic control than those over age 65 years.58 Overall, 44.3% of people with diabetes had A1C above 7.0%.59 Of those over 65, 25.6% had A1C above 7.0%, compared with 47.9% of patients under age 65.60
A1C is used as a measure of glycemic control and improved glycemic control lowers the risk of diabetic complications.61 Cardiovascular disease is a major cause of morbidity and mortality in type 2 diabetes, leading to a 2- to 4-fold increase risk of cardiovascular events and a 3-fold risk in cardiovascular mortality. Large studies have demonstrated reduced cardiovascular events after improved glycemic control with long-term follow-up.62