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Childhood Predictors of Adult Acute Insulin Response and Insulin Action

, MD, , MD, PHD, , MD, DRPH, , MD

Diabetes Care

American Diabetes Association

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      Abstract

      OBJECTIVE

      Because declines in acute insulin response (AIR) and insulin action ( M) predict development of type 2 diabetes, we sought to determine childhood factors that predict insulin action and AIR using longitudinal data from young Pima Indian adults with normal glucose regulation.

      RESEARCH DESIGN AND METHODS

      Predictors of adult M, measured by the euglycemic-hyperinsulinemic clamp, and AIR, measured after a 25-g glucose bolus, were assessed in 76 individuals from a set of childhood data (BMI, systolic blood pressure [sBP] and diastolic blood pressure, cholesterol, fasting and 2-h insulin, and glucose levels during an oral glucose tolerance test).

      RESULTS

      After adjustment for sex, adult percent body fat, adult and childhood age, childhood BMI, and sBP were negative and independent predictors of adult M. A 5 kg/m 2 increase in childhood BMI was associated with a 7.4% decrease in adult insulin action (95% CI −12.7 to −1.8%, P = 0.01) and a 10-mmHg increase in childhood sBP with a 5.0% decrease in adult M (95% CI −8.4 to −1.4%, P = 0.007). After a similar adjustment with M as an additional covariate, childhood 2-h insulin was a positive predictor of adult AIR such that a 25% increase predicted a 7.3% increase in adult AIR (95% CI 1.5–13.5%, P = 0.014).

      CONCLUSIONS

      Childhood insulin response during an oral glucose challenge predicts adult AIR, indicating that β-cell capacity may be set early in life. Childhood measures related to adiposity predict adult insulin action, which may reflect common underlying mechanisms that may be amenable to modification through programs targeting prevention or treatment of childhood obesity.

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      Most cited references 27

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      Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

      Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
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          The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study.

          Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance, but how long these benefits extend beyond the period of active intervention, and whether such interventions reduce the risk of cardiovascular disease (CVD) and mortality, is unclear. We aimed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes, diabetes-related macrovascular and microvascular complications, and mortality. In 1986, 577 adults with impaired glucose tolerance from 33 clinics in China were randomly assigned to either the control group or to one of three lifestyle intervention groups (diet, exercise, or diet plus exercise). Active intervention took place over 6 years until 1992. In 2006, study participants were followed-up to assess the long-term effect of the interventions. The primary outcomes were diabetes incidence, CVD incidence and mortality, and all-cause mortality. Compared with control participants, those in the combined lifestyle intervention groups had a 51% lower incidence of diabetes (hazard rate ratio [HRR] 0.49; 95% CI 0.33-0.73) during the active intervention period and a 43% lower incidence (0.57; 0.41-0.81) over the 20 year period, controlled for age and clustering by clinic. The average annual incidence of diabetes was 7% for intervention participants versus 11% in control participants, with 20-year cumulative incidence of 80% in the intervention groups and 93% in the control group. Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group. There was no significant difference between the intervention and control groups in the rate of first CVD events (HRR 0.98; 95% CI 0.71-1.37), CVD mortality (0.83; 0.48-1.40), and all-cause mortality (0.96; 0.65-1.41), but our study had limited statistical power to detect differences for these outcomes. Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention. However, whether lifestyle intervention also leads to reduced CVD and mortality remains unclear.
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            Author and article information

            Affiliations
            From the Obesity and Diabetes Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona.
            Author notes
            Corresponding author: Marie Thearle, thearlem@ 123456mail.nih.gov
            Journal
            Diabetes Care
            diacare
            dcare
            Diabetes Care
            Diabetes Care
            American Diabetes Association
            0149-5992
            1935-5548
            May 2009
            19 February 2009
            : 32
            : 5
            : 938-943
            2671129
            19228868
            1833
            10.2337/dc08-1833
            © 2009 by the American Diabetes Association.

            Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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            Categories
            Original Research
            Cardiovascular and Metabolic Risk

            Endocrinology & Diabetes

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