While there has been a lack of consensus over the years on how best to define, diagnose, and classify type 2 diabetes mellitus, research in identifying risk factors for diabetes has progressed more clearly. It has been known for years that not all populations or persons present with the same risk for diabetes. For example, populations in developing countries as well as disadvantaged and minority populations in more industrialized countries are at much higher risk. Ethnicity, genetics, and lifestyle play an important role in determining a person's risk factors for type 2 diabetes. The importance of risk factor identification is to promote diabetes screening to initiate prevention measures. Early detection and treatment of type 2 diabetes enhances prevention of microvascular and macrovascular complications associated with this disease.
Several terms require definition as a basis for this article. Risk factors are those aspects of an individual's lifestyle, environment, or genetic traits that are known through epidemiologic study to be associated with occurrence of disease. Prevalence of disease is the number of people known to have the disease (in this case, type 2 diabetes), whether diagnosed or undiagnosed, at a particular time. Incidence refers to the number of people diagnosed with the disease for the first time within a specific time frame.1
Identification of risk factors for type 2 diabetes has been challenging because the genetic and lifestyle factors are interrelated and associated with insulin resistance and metabolic conditions.2-3 These interrelationships are depicted in Fig 1. Groups at highest risk are those persons with a strong family history, persons of older age, those who are obese, and those who are physically inactive. Type 2 diabetes is known to be more predominant in the Native American, Hispanic American, African American, Pacific Islander, and Asian American populations versus those from European descent.2 Since type 2 diabetes is characterized by insulin resistance, people with this disease have the associated metabolic abnormalities, such as hypertension, elevated triglycerides, and low HDL cholesterol, that are also identified as risks factors for type 2 diabetes.3 Women with a history of gestational diabetes mellitus, or who delivered a baby weighing more than 9 lbs., have greater risk for developing type 2 diabetes as well as persons with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG).1,2,4 The greater the number of risk factors an individual has, the greater the chance of developing type 2 diabetes and its associated complications. This article will highlight the more traditional risk factors for diabetes.
It is well accepted that type 2 diabetes is an inherited condition. Though a specific gene has yet to be found, the nearly 100% concordance rates of diabetes seen in identical twins, the aggregation in families, and the high rates seen in ethnic and racial populations lend strong support for this hypothesis. The Framingham Offspring Study found that the risk for type 2 diabetes among offspring with a single parent with diabetes was 3.5 fold greater, and for those with two diabetic parents was 6-fold greater when compared with offspring without parental diabetes.5 No differences were noted in maternal versus paternal risk of transmission, though interestingly the offspring with maternal diabetes were more likely to have milder forms of glucose intolerance as compared to paternal transmission.
Type 2 diabetes has been known for years as "adult onset," or "maturity-onset," emphasizing that the prevalence of type 2 diabetes increases with age. Of persons 65 years or older, 18.4% of all people in this age group have diabetes.1 Many surveys report a leveling off or slight decline at age 75 or greater.6 It is noteworthy that in the past, the age of 45 years has been used as an important cut-off point in estimating the prevalence of diabetes. However, in the last eight years, younger adults between the ages of 30-39 have had a startling 70% rise in type 2 diabetes.1 Rates for the next age group, 40-49 years, rose a dramatic 40%. These startling statistics are blamed on current lifestyle patterns that result in excess body weight and less physical activity.
Minorities in the United States exhibit higher prevalence for diabetes (2-6 times greater than that of white persons)7. The Third National Health and Nutrition Survey—1988-1994 (NHANES III) showed the prevalence rate of diabetes to be 1.7 times higher for non-Hispanic blacks than for whites of similar age.1,6 Controlling for obesity did not affect this increased risk.7 One in four black women aged 55 years or older has diabetes. This is twice the rate for age matched white women. Black females have the highest diabetes related deaths compared with other minorities.1
All Hispanic populations, who comprise the fastest growing minority population in the United States, have greater prevalence rates of type 2 diabetes than non-Hispanic whites.6 Statistics vary depending on the communities studied. Overall, diabetes prevalence rates for Mexican-Americans are estimated at 2 to 5 times that of the non-Hispanic white population, with the greatest prevalence rates found for Puerto Ricans and Hispanics living in the southwest, where half of the adults are affected in some cities.6-8 Limited data are available for prevalence rates for Asian Americans and Pacific Islanders.
According to the Centers for Disease Control and Prevention (CDC), Native Americans have a disproportionately higher prevalence of diabetes—2.8 times that of whites of similar age.7,9 Indeed, the highest prevalence of diabetes in the world has been found among the Pima Indians in Arizona, where approximately 1 of every 2 adults has type 2 diabetes. The CDC study of all Native Americans across the United States conducted between 1990-1997 reported that the prevalence of diabetes increased almost 30% during that time period. These increases were evident across all age groups.9 But even within the high risk populations differences in rates of type 2 diabetes may vary depending on modifiable risk factors such as exercise and weight. For example, the prevalence of type 2 diabetes is six times higher in the Pima Indians living in Arizona than the Pima Indians living in Rural Mexico. One explanation may be that the mean body mass index is 8 kg/m2 greater among the Pima Indians living in Arizona.3
These minority populations are at higher risk, not simply because of their family history and genetic heritage, but because of the increased number of environmental risk factors they exhibit from having "westernized" and taken on the American habits of high calorie diets and sedentary lifestyle.7,9 Other contributing factors, such as lower economic status and access barriers to health care, may negatively impact these groups.7-8 This remains an understudied topic. NHANES III data were examined for racial and ethnic differences in health outcomes for persons with type 2 diabetes.10 Though small differences by race and ethnicity were found in health care access and utilization, along with health outcomes, the most striking finding was the overwhelming suboptimal health status for all diabetics, regardless of race or ethnicity. Socioeconomic status was not a major variable; rather a multiplicity of factors impacted these outcomes.
GESTATIONAL DIABETES MELLITUS (GDM)
Women who have a history of GDM are at greater risk for future diabetes as are their children. Gestational diabetes is defined as any degree of glucose intolerance with its onset or first recognition occurring during pregnancy.11 This definition does not exclude the possibility that undiagnosed glucose intolerance may have preceded the pregnancy. The incidence of GDM averages around 4% of all US pregnancies, though the range is much wider (1-14%) depending on the racial or ethnic groups studied, as well as the prevalence of obesity.12-13 The progression from GDM to diabetes may be partly explained by more universal screening and detection along with the trend for older women to have children.14 The Nurses Health Study examined pregravid determinants of GDM. A family history of diabetes, advanced maternal age, nonwhite ethnicity, higher BMI, weight gain in early adulthood, and cigarette smoking were found to predict a woman's risk for GDM.13
Rates of progression of GDM to diabetes varies, with a 5% risk of type 2 diabetes during the 3-6 month postpartum period, increasing up to 47% at 5-year follow-up.15 Review of additional studies reported a 40% occurrence of diabetes at 15 years in women with prior GDM.1,15 The development of postpartum diabetes is influenced by the degree of obesity prior to pregnancy, the need for insulin treatment during pregnancy, and higher glucose readings during oral glucose tolerance testing.15 Ethnicity also strongly affects progression to diabetes after a GDM pregnancy, with high-risk ethnic groups often reporting 50% of women becoming diabetic within 5 years.14 Of course, the confounding variables of obesity and physical inactivity reported in these ethnic groups, as well as in all women, affect progression to diabetes.
IMPAIRED FASTING GLUCOSE (IFG) and IMPAIRED GLUCOSE TOLERANCE (IGT)
The American Diabetes Association defines IFG and IGT as an intermediate category between normoglycemia and diabetes. Criteria for IFG include individuals with a fasting blood glucose level of 110 mg/dl to 125 mg/dl. IGT is determined from a 2 hour oral glucose tolerance test reading of ≥140 mg/dl but <200 mg/dl.11 Individuals with IGT demonstrate normal glycemic levels throughout most of their daily lives, with the metabolic impairment only noted during glucose tolerance testing. IGT indicates a higher than normal risk of progression to type 2 diabetes, ranging from 2.3 to 11% per year, especially among nonwhite racial and ethnic groups. Prevalence is greater among women in each minority group.6,7,11 Insulin resistance and subsequent IGT are directly involved in the pathogenesis of diabetes. Data from six prospective studies among diverse populations revealed that the strongest predictors of progression from IGT to type 2 diabetes were elevated fasting and 2-hour post challenge glucose levels.16 The detection of IGT is particularly significant since it signals long standing insulin resistance and is a strong risk factor for type 2 diabetes.
Insulin resistance is a defect in the ability of insulin to take up glucose into the muscle cell. Despite being genetically determined, it is greatly aggravated by obesity and physical inactivity.17 During the initial phases of insulin resistance, the pancreatic beta cells are able to maintain normal glycemic control through an increased production of insulin, thereby making these individuals hyperinsulinemic.18-19 However, when individuals can no longer maintain normal glycemia from this compensatory mechanism, they progress to development of type 2 diabetes.18
Research suggests that insulin resistance is a multi-system disorder that is correlated with multiple metabolic abnormalities. It is not surprising that those individuals who are insulin resistant share the same risk factors as those who are at risk for type 2 diabetes. Indeed, insulin resistance predisposes individuals to both diabetes and CVD.18-20 Factors that contribute to insulin resistance are genetics,21 obesity,22 physical inactivity,23 and age.24 Abdominal obesity often accompanies insulin resistance.25 Although there is a strong correlation with insulin resistance and obesity, not all obese people are insulin resistant.26-27 Metabolic risk factors that commonly occur in persons with insulin resistance are hyperinsulinemia, atherogenic dyslipidemia (elevated triglycerides and low HDL-C), glucose intolerance, hypertension, prothrombotic state, hyperuricemia, and polycystic ovary syndrome.19,20,28 The clinical picture of insulin resistance is depicted in Fig 1. Refer also to Quinn's excellent description of the three stages of insulin resistance in the pathogenesis of type 2 diabetes in the lead article of this issue.
OBESITY AND PHYSICAL INACTIVITY
An estimated 97 million US adults are overweight (body mass index (BMI = 25-29.9 kg/m2) or obese (BMI 30 kg/m2 or gt;).29 Despite current recommendations to exercise at a moderate level for 30-45 minutes on most days of the week, 75% of US adults engage in minimal physical activity (such as walking only 15 to 20 minutes a day on a regular basis) or less.30 These life habits, along with the aging of the population, contribute to the growing prevalence of diabetes.31 Obesity alone, especially abdominal adiposity, is a major determinant of the development of type 2 diabetes, causing it to occur at an earlier age.32 When obesity is compounded by physical inactivity, the risk for type 2 diabetes dramatically increases.33 People who are obese and have insulin resistance can increase insulin sensitivity by weight loss; however those people who are obese without insulin resistance do not improve their insulin sensitivity with similar weight loss.34 Mechanisms for the improvement in insulin sensitivity with weight loss are complex and not completely understood at this time.35-36
Limited data in men with type 2 diabetes show that a low level of physical activity is an independent predictor of all cause mortality.37-39 Exercise increases insulin sensitivity and glucose tolerance, as well as improves blood lipid profiles in persons with type 2 diabetes.40-42 Exercise as an adjunct to diet yields greater and more sustained weight loss in obese subjects with type 2 diabetes43 and exercise improves insulin sensitivity and reduces body weight.44 The combination of weight loss and exercise enhances insulin sensitivity and improves glucose control, thus facilitating the risk reduction in type 2 diabetes.
In summary, the profile of individuals most at risk for developing type 2 diabetes is clear. Although genetic predisposition exhibits the strongest influence, attention to the modifiable risk factors is strongly warranted. It is clear that physical activity and weight management have a positive influence on retarding or halting the progression to type 2 diabetes. As nurses, our role is to be to be aware of what populations will be at higher risk for developing type 2 diabetes and to be proactive in promoting influential lifestyle habits with the goal of reducing the incidence of IGT and type 2 diabetes and its complications.
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