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Genetic background is important in determining susceptibility to metabolic abnormalities such as insulin resistance and [beta]-cell dysfunction. Islet amyloid is associated with reduced [beta]-cell mass and function and develops in the majority of our C57BL/6J x DBA/2J ([F.sub.1]) male human islet amyloid polypeptide (hIAPP) transgenic mice after 1 yr of increased fat feeding. To determine the relative contribution of each parental strain, C57BL/6J (BL6) and DBA/2J (DBA2), to islet amyloid formation, we studied male hlAPP mice on each background strain (BL6, n = 13; and DBA2 n = 11) and C57BL/6J x DBA/2J [F.sub.1] mice (n = 17) on a 9% (wt/wt) fat diet for 1 yr. At the end of 12 mo, islet amyloid deposition was quantified from thioflavin S-stained pancreas sections. The majority of mice in all groups developed islet amyloid (BL6: 91%, [F.sub.1]: 76%, DBA2: 100%). However, the prevalence (%amyloid-positive islets; BL6:14 [+ or -] 3%, [F.sub.1]: 44 [+ or -] 8%, DBA2: 49 [+ or -] 9%, P < 0.05) and severity (%islet area occupied by amyloid; BL6:0.03 [+ or -] 0.01%, [F.sub.1]: 9.2 [+ or -] 2.9%, DBA2:5.7 [+ or -] 2.3%, p [less than or equal to] 0.01) were significantly lower in BL6 than [F.sub.1] and DBA2 mice. Increased islet amyloid severity was negatively correlated with insulin-positive area per islet, in [F.sub.1] ([r.sup.2] = 0.75, P < 0.001) and DBA2 (re = 0.87, P < 0.001) mice but not BL6 mice (re = 0.07). In summary, the extent of islet amyloid formation in hIAPP transgenic mice is determined by background strain, with mice expressing DBA/2J genes ([F.sub.1] and DBA2 mice) being more susceptible to amyloid deposition that replaces [beta]-cell mass. These findings underscore the importance of genetic and environmental factors in studying metabolic disease. islet amyloid; islet amyloid polypeptide; genetic background; [beta]-cell mass; [beta]-cell dysfunction; insulin secretion

Pancreatic amyloid is found in patients with insulinomas and type 2 diabetes. To study mechanisms of islet amyloidogenesis, we produced transgenic mice expressing the unique component of human islet amyloid, human islet amyloid polypeptide (hIAPP). These mice develop islet amyloid after 12 mo of high-tat feeding. To determine whether we could accelerate the rate of islet amyloid formation, we crossbred our hIAPP transgenic animals with RIP-Tag mice that develop islet tumors and die at 12 wk of age from hypoglycemia. At 12 wk of age, this new line of hIAPP x RIP-Tag mice was heavier (29.7 [+ or -] 1.0 vs. 25.0 [+ or -] 1.3 g, P < 0.05) and had increased plasma glucose levels (4.6 [+ or -] 0.4 vs. 2.9 [+ or -] 0.6 retool/l, P < 0.05) compared with littermate RIP-Tag mice. However, the hIAPP x RIP-Tag mice did not display islet amyloid or amyloid fibrils despite high circulating hIAPP levels (24.6 [+ or -] 7.0 pmol/1). Interestingly, hIAPP x RIP-Tag mice had a longer life span than RIP-Tag mice (121 [+ or -] 8 vs. 102 [+ or -] 5 days, P < 0.05). This increase in life span in hIAPP x RIP-Tag was positively correlated with body weight (r = 0.48, P < 0.05) and was associated with decreased insulin sensitivity compared with RIP-Tag mice. hIAPPXRIP-Tag mice did not develop amyloid during their 4-too life span, suggesting that increased hlAPP secretion is insufficient for islet amyloid formation within such a short time. However, hIAPP x RIP-Tag mice did have an increase in life span that was associated with insulin resistance, suggesting that hIAPP has extrapancreatic effects, possibly on peripheral glucose metabolism. amylin; euglycemic hyperinsulinemic clamp; insulin sensitivity

The journal Diabetes Care has introduced a new feature that links articles to relevant recordings of scientific presentations from the American Diabetes Association Scientific Sessions. This allows readers to gain greater insight into important topics related to diabetes care. The linked presentations are accessible to readers beyond the time of the conference and are free of charge. The first issue to include this feature includes a review and two articles discussing glycemia-related data. This new feature, along with the podcast "Diabetes Care 'On Air,'" aims to enhance the learning experience for readers. [Extracted from the article]

Objective: Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5,145 individuals with overweight/obesity and type 2 diabetes, found no significant differences in all-cause or cardiovascular mortality or morbidity during 9.6 (median) years of intervention. Participants in ILI who lost ≥10% at 1 year had lower risk of composite cardiovascular outcomes relative to DSE. Since effects of ILI may take many years to emerge, we conducted intent-to-treat analyses comparing mortality in ILI over 16.7 years (9.6 years of intervention and then observation) to DSE. In a secondary exploratory analysis, we compared mortality by magnitude of weight loss in ILI relative to DSE.Research Design and Methods: Primary outcome was all-cause mortality from randomization to 16.7 years. Other outcomes included cause-specific mortality, interactions by subgroups (age, sex, race/ethnicity, and cardiovascular disease history), and an exploratory analysis by magnitude of weight loss in ILI versus DSE as reference. Analyses used proportional hazards regression and likelihood ratio.Results: The incidence of all-cause mortality did not differ significantly in ILI and DSE (549 and 589 participants, respectively) (hazard ratio [HR] 0.91 [95% CI 0.81, 1.02]; P = 0.11). There were no significant differences between treatments in cause-specific mortality or within prespecified subgroups. ILI participants who lost ≥10% at 1 year had a 21% reduced risk of mortality (HR 0.79 [95% CI 0.67, 0.94]; P = 0.007) relative to DSE.Conclusions: ILI focused on weight loss did not significantly affect mortality risk. However, ILI participants who lost ≥10% had reduced mortality relative to DSE. [ABSTRACT FROM AUTHOR]

Objective: To conduct post hoc secondary analysis examining the association between change in physical activity. Measured with self-report and accelerometry, from baseline to 1 and 4 years and cardiovascular disease (CVD) outcomes in the Look AHEAD Trial.Research Design and Methods: Participants were adults with overweight/obesity and type 2 diabetes with physical activity. Data at baseline and year 1 or 4 (n = 1,978). Participants were randomized to diabetes support and education or intensive lifestyle intervention. Measures included accelerometry-measured moderate-to-vigorous physical activity (MVPA), self-reported physical activity, and composite (morbidity and mortality) CVD outcomes.Results: In pooled analyses of all participants, using Cox proportional hazards models, each 100 MET-min/week increase in accelerometry-measured MVPA from baseline to 4 years was associated with decreased risk of the subsequent primary composite outcome of CVD. Results were consistent for changes in total MVPA (hazard ratio 0.97 [95% CI 0.95, 0.99]) and MVPA accumulated in ≥10-min bouts (hazard ratio 0.95 [95% CI 0.91, 0.98]), with a similar pattern for secondary CVD outcomes. Change in accelerometry-measured MVPA at 1 year and self-reported change in physical activity at 1 and 4 years were not associated with CVD outcomes.Conclusions: Increased accelerometry-measured MVPA from baseline to year 4 is associated with decreased risk of CVD outcomes. This suggests the need for long-term engagement in MVPA to reduce the risk of CVD in adults with overweight/obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

An introduction is presented din which author discusses articles on topics including focuses on importance to society and health care and those that offer a spectrum of knowledge on a theme, providing insight from basic science to clinical topics.