Samples and data are analyzed from a longitudinal population study conducted from 1965 to 2007 that allows study of the risk factors and effects of diabetes mellitus. Risk factors for obesity, hypertension, and nephropathy are also studied, along with the relationships of these diseases to diabetes and their effects on development of vascular complications and mortality. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. These findings are reported in DK069028 (Genetic epidemiology of diabetes and obesity) and DK069094 (Genetic epidemiology of diabetic complications). Knowledge of diabetes risk factors coming from this and other studies led to the hypothesis that type 2 diabetes could be prevented or delayed in adults at high short-term risk. This hypothesis was confirmed in the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial in which many of the participants and investigators in this project participated. We are now in a long-term follow-up phase, the Diabetes Prevention Program Outcomes Study (DPPOS), to assess long-term success with weight loss, reduction in the incidence of diabetes, and effects on diabetes complications. This study is reported in DK075078 (Prevention of type 2 diabetes). Environmental exposure to arsenic has been implicated as contributing to the risk of type 2 diabetes in other populations. We, therefore, examined effects of urinary concentrations of arsenic species on incident diabetes in a case-control study nested within the longitudinal population study. One-hundred-fifty nondiabetic subjects 25 years old who subsequently developed type 2 diabetes were matched for year of examination and sex to 150 controls who remained nondiabetic for 10 years. There was no significant linear association between urinary arsenic concentration and development of diabetes, but in a post-hoc analysis, persons in the top 3 quartiles of urinary arsenic concentration had 2.14 times the incidence of diabetes as those in the lowest quartile. Therefore, modestly elevated exposure to inorganic arsenic may predict type 2 diabetes in Southwestern American Indians. Larger studies that include measures of speciated arsenic are required for confirmation. We performed another nested case-control study to examine the relationship between serum concentrations of persistent organic pollutants (POPs). The case-control study included 300 persons without diabetes at baseline (median age=24 years);149 subjects subsequently developed diabetes (cases) and 151 remained non-diabetic during 10 years of follow-up (controls). POPs 37 polychlorinated biphenyls (PCBs) and 9 persistent pesticides (PSTs) were measured in serum collected in 1969-1974. Diabetes was diagnosed clinically or by a 2-hour oral glucose test. Odd ratios for diabetes were computed with logistic regression analysis for total PCBs (sum of the 37 congeners), the individual PCB congeners, and individual PSTs. Three of the POPs, PCB66, PCB151, and PCB195, were weakly but positively associated with development of diabetes. In this nested case-control study, we also measured 25-hydroxyergocalciferol 25(OH)D2, 25-hydroxycholecalciferol 25(OH)D3, and vitamin D binding protein. Half of the study participants (82 cases, 68 controls) were 25(OH)D deficient. Median 25(OH)D3 was 18 ng/ml in cases and 20 ng/ml in controls;25(OH)D2 was detectable in 12% of cases and 20% of controls. Odds ratio (OR) for incident diabetes in those with detectable vs. undetectable 25(OH)D2 was 0.50 (95% CI, 0.26-0.98) after adjustment for potential confounders. 25(OH) and vitamin D binding protein were not associated with incident diabetes. Detectable 25(OH)D2, derived from dietary sources, was associated with half the rate of incident type 2 diabetes in this population. Whether this finding is attributable to a direct beneficial effect of 25(OH)D2 or to a protective effect of a healthier diet in general remains to be determined. Other findings related to kidney complications of diabetes are reported in DK069062 (Epidemiology, pathophysiology and treatment of diabetic nephropathy).

Project Start
Project End
Budget Start
Budget End
Support Year
48
Fiscal Year
2013
Total Cost
$141,079
Indirect Cost
City
State
Country
Zip Code
Paddock, Ethan; Looker, Helen C; Piaggi, Paolo et al. (2018) One-Hour Plasma Glucose Compared With Two-Hour Plasma Glucose in Relation to Diabetic Retinopathy in American Indians. Diabetes Care 41:1212-1217
Muller, Yunhua L; Skelton, Graham; Piaggi, Paolo et al. (2018) Identification and functional analysis of a novel G310D variant in the insulin-like growth factor 1 receptor (IGF1R) gene associated with type 2 diabetes in American Indians. Diabetes Metab Res Rev 34:e2994
Hsueh, Wen-Chi; Bennett, Peter H; Esparza-Romero, Julian et al. (2018) Analysis of type 2 diabetes and obesity genetic variants in Mexican Pima Indians: Marked allelic differentiation among Amerindians at HLA. Ann Hum Genet 82:287-299
Vijayakumar, P; Wheelock, K M; Kobes, S et al. (2018) Secular changes in physical growth and obesity among southwestern American Indian children over four decades. Pediatr Obes 13:94-102
Tanamas, Stephanie K; Saulnier, Pierre-Jean; Hanson, Robert L et al. (2018) Serum lipids and mortality in an American Indian population: A longitudinal study. J Diabetes Complications 32:18-26
Tanamas, Stephanie K; Reddy, Sanil P; Chambers, Melissa A et al. (2018) Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population. Pediatr Diabetes 19:622-629
Vijayakumar, Pavithra; Nelson, Robert G; Hanson, Robert L et al. (2017) HbA1c and the Prediction of Type 2 Diabetes in Children and Adults. Diabetes Care 40:16-21
Piaggi, Paolo; Masindova, Ivica; Muller, Yunhua L et al. (2017) A Genome-Wide Association Study Using a Custom Genotyping Array Identifies Variants in GPR158 Associated With Reduced Energy Expenditure in American Indians. Diabetes 66:2284-2295
Grice, Brian A; Nelson, Robert G; Williams, Desmond E et al. (2017) Associations between persistent organic pollutants, type 2 diabetes, diabetic nephropathy and mortality. Occup Environ Med 74:521-527
Grau-PĂ©rez, Maria; Kuo, Chin-Chi; Spratlen, Miranda et al. (2017) The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study. Diabetes Care 40:46-53

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