Established Diabetes Risk Factors Research Articles

Polymorphisms within the Protein Tyrosine Phosphatase 1B (PTPN1) Gene Promoter: Functional Characterization and Association with Type 2 Diabetes and Related Metabolic Traits

Protein tyrosine phosphatase 1B (PTPN1) dephosphorylates insulin receptors and attenuates insulin signaling. Polymorphisms in the coding sequence of PTPN1 have been variably associated with type 2 diabetes (T2D). We hypothesized that variations within the PTPN1 promoter might contribute to the development of T2D and related metabolic traits. We screened 2.0 kb of PTPN1 promoter in 174 T2D patients and 412 controls using PCR and denaturing HPLC. Association analysis was performed between diabetes and related traits and single-nucleotide polymorphism genotypes. We functionally tested 2 variants (-1023C>A and -51delA) by measuring their influence on luciferase activity in HepG2 cells and performing the electrophoretic mobility shift assay (EMSA). One common (-1023C>A) and 6 rare (-51delA, -451A>G, -467T>C, -1045G>A, -1286-3bp-del, and -1291-9bp-del) variants were identified in the PTPN1 promoter. The -1023(C) allele had significant association with T2D that disappeared after we adjusted for established diabetes risk factors. The alleles of -1023C>A and -51delA variants did not show significant effects on the biochemical markers after adjustment for established diabetes risk factors in the nondiabetic and diabetic groups separately. The -51delA variant decreased luciferase gene expression in HepG2 cells by 2-fold. EMSA revealed a weaker binding of -51delA to specific protein family proteins compared with the A allele. The -1023C>A variant had no influence in either experiment. The PTPN1 promoter variants -1023C>A and -51delA (which appears to be functional) were not associated with T2D or related traits in this study but must be investigated in a larger population to reveal any potential metabolic association.

The role of depression and anxiety in onset of diabetes in a large population-based study

Objective Recent research has shown that depression may predict incident diabetes. The aims of the study are to investigate if symptoms of depression and anxiety precede the onset of diabetes or vice versa and to examine if mediating factors may explain such associations. Methods A prospective population-based study ( N=37,291) investigating the associations between symptoms of depression/anxiety and diabetes was conducted. Results Individuals reporting symptoms of depression and anxiety at baseline had increased risk of onset of type 2 diabetes at 10-year follow-up. No gender differences were found. The analyses did not reveal underlying factors that mediated the association. Baseline diagnosis of diabetes was not associated with subsequent symptoms of anxiety or depression among males or females. Conclusion Diabetes did not predict symptoms of depression or anxiety. Symptoms of depression and anxiety emerged as significant risk factors for onset of type 2 diabetes independent of established risk factors for diabetes, such as socioeconomic factors, lifestyle factors, and markers of the metabolic syndrome. The comorbidity between depression and anxiety may be the most important factor.

Retrospective Analysis of Diabetes Risk in Elderly Patients With Dementia in Olanzapine Clinical Trials

The objective of this study was to evaluate the association of established risk factors for treatment-emergent diabetes (TED) among patients over 65 years of age with dementia who received treatment with olanzapine. This was a post hoc analysis of data pooled from seven olanzapine clinical trials, which included patients over 65 years of age with dementia. The association of established risk factors for TED was evaluated using categorical and time-to-event analysis. TED was defined as two casual (fasting or nonfasting) glucose values > or =200 mg/dL at any time after baseline or one casual glucose value > or =200 mg/dL at the final visit, initiation of antidiabetic medication, or new clinical diagnosis of diabetes. Elderly patients subsequently identified with TED (N = 29, 2.1%) had similar baseline body mass indices (24 kg/m(2)) and were similar in age (82 versus 80 years) to those who did not have TED. Cox proportional hazards model identified only elevated casual glucose (> or =140 mg/dL) measure at baseline to be significantly associated with the development of TED (hazard ratio [HR] = 11.2, p <0.0001) in this elderly cohort. Other clinical risk factors, like body mass index > or =25 (HR = 0.86), 7% weight gain (HR = 2.26), and antipsychotic treatment (HR = 1.36) were not significant. In elderly patients with dementia enrolled in olanzapine clinical trials, an elevated casual glucose (> or =140 mg/dL) at baseline was the only risk factor significantly associated with subsequent development of TED. Risk of diabetes in these studies was not significantly associated with antipsychotic treatment group assignment.

Alcohol consumption and other risk factors for self‐reported diabetes among middle‐aged Japanese: a population‐based prospective study in the JPHC study cohort I

Few prospective studies have examined the relationship between lifestyle characteristics and the incidence of diabetes mellitus in an Asian general population. This study was undertaken to evaluate the risk factors for Type 2 diabetes in a population-based prospective study of middle-aged Japanese. We investigated 12,913 men and 15,980 women, aged 40-59 years at baseline (year 0), who participated in the Japan Public Health Center-based prospective study on cancer and cardiovascular diseases (JPHC Study) Cohort I. The participants were followed for up to 10 years. Incident cases of diabetes were identified by self-reporting of a physician's diagnosis on two questionnaires sent to each participant, one at year 5 and the second at year 10. During the 10-year follow-up, 703 men and 482 women reported newly diagnosed diabetes. Age, body mass index (BMI), family history of diabetes and cigarette smoking were independent risk factors in both genders by multivariate analysis. Among men with a BMI < or = 22 kg/m2, a significant positive association was observed between the diabetes incidence and moderate (23.0 < 46.0 g/day) to high (> 46.0 g/day) alcohol consumption, odds ratio 1.91 (95% CI, 1.05-3.46) and 2.89 (1.63-5.11), respectively. Among men with a BMI > 22 kg/m2, a small non-significant increase in odds ratio was observed with alcohol consumption. Established risk factors for diabetes in western populations were also identified as predictors of the disease among Japanese. Moderate to high alcohol consumption was positively associated with the incidence of diabetes in Japanese lean (BMI < or = 22 kg/m2) men.

Weight Change and the Risk of Gestational Diabetes in Obese Women

Obesity is an established risk factor for gestational diabetes. It is not known whether this risk might be reduced through weight loss between pregnancies. We sought to determine whether weight loss between pregnancies reduced the risk of gestational diabetes among obese women. We conducted a population-based cohort study of 4102 women with 2 or more singleton live births in Washington State between 1992 and 1998. All subjects were nondiabetic and obese (at least 200 lbs) at their first birth during these years. Weight change was calculated as the difference between prepregnancy weight for the 2 pregnancies. We estimated relative risks of gestational diabetes at the subsequent delivery through stratified analyses and Mantel-Haenszel estimates. Thirty-two percent of women lost weight between pregnancies, with a mean weight loss of 23 lbs. Women who lost at least 10 lbs between pregnancies had a decreased risk of gestational diabetes relative to women whose weight changed by less than 10 lbs (relative risk = 0.63; 95% confidence interval = 0.38-1.02, adjusted for age and weight gain during each pregnancy). Of the 61% of women who gained weight between pregnancies, the mean weight gain was 22 lbs. Women who gained at least 10 lbs had an increased risk of gestational diabetes (1.47; 1.05-2.04). Even moderate changes in prepregnancy weight can apparently affect the risk of gestational diabetes among obese women. This may offer further motivation for interventions aimed at reducing obesity among women of reproductive age.

Symptoms of depression as a risk factor for incident diabetes: findings from the National Health and Nutrition Examination Epidemiologic Follow-up Study, 1971-1992.

Symptoms of depression may predict incident diabetes independently or through established risk factors for diabetes. US men and women aged 25-74 years who were free of diabetes at baseline (n = 6,190) were followed from 1971 to 1992 (mean, 15.6 years; standard deviation, 6) for incident diabetes. Depressive symptoms were measured by using the General Well-Being Depression subscale and were categorized to compare persons with high (9%), intermediate (32%), and low (59%) numbers of symptoms. The incidence of diabetes was highest among participants reporting high numbers of depressive symptoms (7.3 per 1,000 person-years) and did not differ between persons reporting intermediate and low numbers of symptoms (3.4 and 3.6 per 1,000 person-years, respectively) (p < 0.01 for high vs. low). In the subset of participants with less than a high school education (a marker of low socioeconomic status), the risk of developing diabetes was three times higher (95% confidence interval: 2.0, 4.7) for persons reporting high versus low numbers of depressive symptoms. These results persisted following adjustment for established diabetes risk factors. Depressive symptoms had no impact on diabetes incidence among persons with at least a high school education. Results suggest an independent role for depressive symptoms in the development of diabetes in populations with low educational attainment.

Bienestar: a diabetes risk-factor prevention program.

The Bienester Health Program, a diabetes risk-factor prevention pilot program, targeted fourth grade Mexican American children. The primary goals are to decrease the two established risk factors for diabetes--overweight and dietary fats. Since the health program is based on Social Cognitive Theory, on social systems structure, and on culturally relevant material, it considers the child's social systems on both its health program and process evaluation. Learning activities were developed for four social systems that potentially influence children's health behaviors (parent, classroom, school cafeteria, and after-school care). Preliminary results show that the Bienestar Health Program significantly decreased dietary fat, increased fruit and vegetable servings, and increased diabetes health knowledge.