Retrospective cohort study to determine the effect of metformin on survival of diabetic patients with pancreatic adenocarcinoma

Background: Pancreatic cancer is the fourth most common cause of cancer death in the United States. Despite advances in cancer treatment, prognosis of pancreatic cancer remains extremely poor with survival rates of 24% and 5% in 1 and 5 years, respectively. Many patients with pancreatic cancer have a history of diabetes and are treated with various antidiabetic regimens including metformin. In multiple retrospective studies, metformin has been associated with decreased risk of cancer and cancer-related mortality. Metformin has also been reported to inhibit the growth of cancer cells, both in vitro and in vivo.^ Methods: We conducted a retrospective cohort study to examine the survival benefit of metformin in diabetic patients with pancreatic cancer at MD Anderson Cancer Center (MDACC). A dataset of 397 patients who carried the diagnosis of "Diabetes Mellitus" and "Pancreatic Cancer" at MD Anderson were screened for this study. ^ Results: Mean age of patients at diagnosis of cancer was 64.0 ± 8.7 years (range 37-84). The majority of the patients were male (65.6%) and of Caucasian race (78.5%). The most common antidiabetic regimen used were insulin and metformin (in 39.1% and 38.7%, respectively). Patients' cancer were staged as resectable in 34.1%, locally advanced unresectable in 29.1%, and disseminated disease in 36.7% of cases. Overall 1-year and 3-year survival rates for all stages combined were 51.8% and 7.6%, respectively. Earlier stage, metformin use, low CA19-9 level, better ECOG performance status, surgical intervention, negative surgical margins, and smaller tumor size were associated with longer survival. Metformin use was associated with a 33% decrease in risk of death (HR: 0.67; 95% CI: 0.51-0.88). Multivariate Cox proportional hazard regression showed hazard ratio of 1.77 (95% CI 1.49-2.10) for cancer stage, 0.65 (95% CI 0.49-0.86) for metformin use, and 1.68 (95% CI 1.26-2.23) for CA 19-9 level above population median. ^ Conclusion: Our study suggests that metformin may improve the outcome in diabetic patients with pancreatic cancer independently of other known prognostic factors. Pancreatic cancer carries extremely poor prognosis; metformin may provide a suitable adjunct therapeutic option for pancreatic cancer in patients with and without diabetes mellitus.^

Cardiovascular disease risk factors in Hispanic children identified through a diabetic proband

Prevalence and mortality rates for non-insulin dependent (Type II) diabetes mellitus are two to five times greater in the Mexican-American population than in the general U.S. population. Diabetes has been associated with risk factors which increases the likelihood of developing atherosclerosis. Relatives of noninsulin dependent diabetic probands are at increased risk of developing diabetes; and offspring of diabetic parents are at greater risk. Elevation in risk factor levels clearly began to develop prior to adulthood. Therefore an excess of these risk factors are expected among offspring and relatives of diabetics.^ The purposes of this study were to describe levels of risk factors within a group of Mexican American children who were identified through a diabetic proband, and to determine if there was a relationship between risk factor levels and heritability. Data from three hundred and seventy-six children and adolescents between the ages of 7 and 13 years, inclusively, were analyzed. These children were identified through a diabetic proband who participated in the Diabetes Alert Study. This study group was compared to a representative sample of Mexican American children, who participated in the Hispanic Health and Nutrition Examination Survey.^ For females, there were statistically significant associations between upper body fat distribution and increased systolic and diastolic blood pressure after adjusting for age and measures of fatness. Body mass index was positively related to and explained a significant portion of the variability in systolic blood pressure, total cholesterol, and HDL-cholesterol, for males only. No relationship was found between degree of relationship to the diabetic proband and risk factor levels. The most likely explanations for this were insufficient sample size to detect differences, and/or incomplete ascertainment of pedigree information.^ Although there was evidence that these Mexican American children are fatter and have more central fat distribution than non-Hispanic children, there is no evidence of increased risk for diabetes and/or cardiovascular disease at these ages. ^

DIABETIC RETINOPATHY IN NON-INSULIN-DEPENDENT DIABETES MELLITUS IN BLACK WOMEN: A DESCRIPTIVE STUDY OF RISK FACTORS

This cross-sectional study examines the prevalence of selected potential risk factors by stage of diabetic retinopathy (DR) among Black American women with non-insulin-dependent diabetes mellitus (NIDDM) followed at a university diabetes clinic. DR was assessed by ophthalmoscopy and five-field retinography, and graded on counts of microaneurysms, hemorrhages and/or exudates, and presence of proliferative DR. Prevalence of other vascular diseases was assessed from medical records. Potential risk factors included age, known duration of diabetes, type of hypoglycemic treatment, concentrations of random capillary blood glucose, glycosylated hemoglobin, urine protein and fibrinogen, body mass index, and blood pressure. Prevalence of these risk factors is reported for three categories: No DR, mild background DR, severe background or proliferative DR (including surgically treated DR). Duration, age at diagnosis and treatment of diabetes, concentration of urine protein and average blood glucose, hypertension and cardiovascular disease were significantly associated with DR in univariate analysis. The covariance analysis employed stratification on duration, age at diagnosis and therapy of diabetes. The highest DR scores were calculated for those diagnosed before age 45, regardless of duration, therapy, or average blood glucose. Only individuals diagnosed before age 45 had high blood glucose concentrations in all categories of duration. These findings suggest that in this clinic population of Black women, those diagnosed with NIDDm before age 45 who eventually required insulin treatment were at the greatest risk of developing DR and that longterm poor glucose control is a contributing factor. These results suggest that greater emphasis be placed on this subgroup in allocating the limited resources available to improve the quality of glucose regulation, particularly through measures affecting compliance behavior.^ Findings concerning the association of DR with concentration of blood glucose and urine protein, blood pressure/hypertension and weight were compared with those reported from American Indian and Mexican American populations of the Southwestern United States where prevalence of NIDDM, hypertension and obesity is also high. Additional comparative analyses are outlined to substantiate the preliminary finding that there are systematic differences between these ethnic populations. ^

Soft tissue oral wound healing in diabetic patients

This prospective observational cohort study investigated whether diabetic dental patients with poor glycemic control experience a higher risk of post-operative complications and diminished wound healing abilities after an oral surgical procedure such as implant placement. This study compared soft tissue oral wound healing complications between poorly controlled diabetic patients, well controlled diabetic patients and non-diabetic patients following surgical implant placement in the mandible with a total of 131 patients. A one week post-surgical follow-up visit involved an oral wound examination that consisted of evaluating for edema, erythema, exudate, oral pain, problems with flap closure, infection, and hematoma. Analyses were performed to determine significance differences in frequency of oral wound complications between the 3 diabetic groups. Two-by-two contingency tables using chi-square analysis were used to evaluate for significant differences in the proportion of each post-operative oral wound healing complication. This was done separately between non-diabetics and diabetics and between well-controlled and poorly controlled diabetics to calculate odds ratios. Confidence intervals were also calculated. This preliminary study showed that many of the complications were found not to be associated with diabetic status. Other complications such as edema and problems with flap closure were found to be less likely to occur in diabetics compared to non-diabetics and even in poorly controlled diabetics when compared to well-controlled diabetics. The results did not support the hypothesis that diabetic dental patients experience a higher risk than non-diabetic patients of post-operative soft tissue oral wound complications.^

Risk factors for diabetic retinopathy in Mexican Americans in Starr County, Texas

The prevalence of diabetes in Mexican Americans is disproportionately higher than in non-Hispanic whites. The rate of diabetic retinopathy resulting from prolonged diabetes is also greater in Mexican Americans than in non-Hispanic whites. A longitudinal study was carried out on data collected from Mexican Americans in Starr County, Texas to assess the association between socioeconomic and acculturation factors with diabetic retinopathy prevalence, incidence, and progression in those free of diabetic retinopathy or who had only early non-proliferative diabetic retinopathy. A multivariable analysis was done. ^ The incidence rate was 12.78 cases per year and the progression rate was 8.55 cases per year. The baseline characteristics of the population revealed that more people with occupations synonymous with lower income jobs like trade workers and machine operators had early non-proliferative diabetic retinopathy. A multivariable analysis revealed that those with early non-proliferative diabetic retinopathy were more likely to have been born in Mexico as compared to those free of diabetic retinopathy. Surprisingly, a multivariable analysis also showed that those that progressed in diabetic retinopathy disease status were more likely to have been employed as compared to those that did not. ^ This analysis reveals that Mexican Americans are heterogeneous in socioeconomic and acculturation factors that may be used to deter the incidence and progression of diabetic retinopathy severity. These findings could be targeted to create culturally sensitive intervention programs that will improve the detection and treatment of diabetic retinopathy in the work arena in addition to programs that will impact those that do not work. Workplace preventative health screenings and dissemination of language-specific informational brochures is warranted to curb the rates of progression in those employed. ^ A limitation of this study is the narrow surrogates used for assessing socioeconomic and acculturation status. To fully evaluate these variables, a study using a questionnaire with a multitude of surrogates for socioeconomic and acculturation factors should be employed.^

Health outcomes, quality improvement and cost-effectiveness of the Community Diabetes Education (CoDE) program: Results of a randomized controlled trial

The objectives of this dissertation were to evaluate health outcomes, quality improvement measures, and the long-term cost-effectiveness and impact on diabetes-related microvascular and macrovascular complications of a community health worker-led culturally tailored diabetes education and management intervention provided to uninsured Mexican Americans in an urban faith-based clinic. A prospective, randomized controlled repeated measures design was employed to compare the intervention effects between: (1) an intervention group (n=90) that participated in the Community Diabetes Education (CoDE) program along with usual medical care; and (2) a wait-listed comparison group (n=90) that received only usual medical care. Changes in hemoglobin A1c (HbA1c) and secondary outcomes (lipid status, blood pressure and body mass index) were assessed using linear mixed-models and an intention-to-treat approach. The CoDE group experienced greater reduction in HbA1c (-1.6%, p<.001) than the control group (-.9%, p<.001) over the 12 month study period. After adjusting for group-by-time interaction, antidiabetic medication use at baseline, changes made to the antidiabetic regime over the study period, duration of diabetes and baseline HbA1c, a statistically significant intervention effect on HbA1c (-.7%, p=.02) was observed for CoDE participants. Process and outcome quality measures were evaluated using multiple mixed-effects logistic regression models. Assessment of quality indicators revealed that the CoDE intervention group was significantly more likely to have received a dilated retinal examination than the control group, and 53% achieved a HbA1c below 7% compared with 38% of control group subjects. Long-term cost-effectiveness and impact on diabetes-related health outcomes were estimated through simulation modeling using the rigorously validated Archimedes Model. Over a 20 year time horizon, CoDE participants were forecasted to have less proliferative diabetic retinopathy, fewer foot ulcers, and reduced numbers of foot amputations than control group subjects who received usual medical care. An incremental cost-effectiveness ratio of $355 per quality-adjusted life-year gained was estimated for CoDE intervention participants over the same time period. The results from the three areas of program evaluation: impact on short-term health outcomes, quantification of improvement in quality of diabetes care, and projection of long-term cost-effectiveness and impact on diabetes-related health outcomes provide evidence that a community health worker can be a valuable resource to reduce diabetes disparities for uninsured Mexican Americans. This evidence supports formal integration of community health workers as members of the diabetes care team.^

From foot-draggers to strategic counter-partners : the dynamics of U.S. and Chinese policies for tackling climate change

As can been seen from the U.S.'s non-ratification of the Kyoto Protocol, together with the negotiations toward the post-Kyoto Protocol framework, the U.S. and China have been quarrelling over their responsibilities and have contradicted one another over the introduction of compulsory domestic greenhouse gases emission reduction targets. Therefore, for a long time, it has been argued that the controversy between the two countries has hindered the process of forging an international agreement to deal with climate change. On the other hand, Sino-U.S. bilateral cooperation on climate change has significantly increased in recent years in summit talks and their Strategic & Economic Dialogue (S&ED), especially after the 15th Conference of Parties (COP) of the United Nations Framework Convention on Climate Change (UNFCCC) in Copenhagen, one of whose aims was to facilitate positive negotiations for the post-Kyoto Protocol agreement. Analyzing this in the light of recent developments, we find that the U.S. and China have tended to address climate change and related issues from a pluralistic viewpoint and approach, by regarding the achievement of bilateral cooperation and global agreements as their common strategic objective.

An iPhone-based application for promoting type 2 diabetic patients self- management towards healthy lifestyle habits

— In 2000, according to the World Health Organization, at least 171 million people, 2.8% of the population worldwide, suffered from diabetes. The Centres for Disease Control has defined it as an epidemic disease. Its incidence is increasing rapidly, and it is estimated that by 2030 this number will almost double. Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. Diabetes is a chronic condition that occurs when pancreas does not assure enough insulin secretion or when the body does not consume the insulin produced. Insulin is a hormone that regulates blood sugar. The effect of uncontrolled diabetes is the hyperglycaemia (blood sugar), which eventually seriously damage many organs and systems, especially the nerves and blood vessels. Diabetes type 2 (most common type of diabetes) is highly correlated with elderly people, obesity or overweight. Promoting a healthy lifestyle helps patients to improve their quality of life and in many cases to avoid complications related to the disease. This paper is intended to describe an iPhone-based application for self-management of type 2 diabetic patients, which allow them improving their lifestyle through healthy diet, physical activity and education