Pre-existing Type 2 Diabetes Research Articles

Type 2 diabetes and colorectal cancer survival: The multiethnic cohort.

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre-existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all-cause and 678 CRC-specific deaths after a mean follow-up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC-specific and all-cause survival while adjusting for known confounders. Overall, CRC-specific survival was not associated with pre-existing T2D (HR = 0.84; 95% CI = 0.67-1.07). However, a significant interaction was seen for comorbidity (pinteraction =0.03) with better survival among those without pre-existing conditions (HR = 0.49; 95% CI = 0.25-0.96) while no association was seen in patients with comorbid conditions. All-cause mortality was also not related to pre-existing T2D (HR = 1.11; 95% CI = 0.98-1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19-1.56). Stratification by T2D duration suggested higher CRC-specific and all-cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre-existing T2D had no influence on disease-specific and all-cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.

Comparison of regional fat measurements by dual-energy X-ray absorptiometry and conventional anthropometry and their association with markers of diabetes and cardiovascular disease risk

Background/Objectives:Fat distribution is a strong and independent predictor of type 2 diabetes (T2D) and cardiovascular disease (CVD) and is usually determined using conventional anthropometry in epidemiological studies. Dual-energy X-ray absorptiometry (DXA) can measure total and regional adiposity more accurately. Nonetheless, whether DXA provides more precise estimates of cardiovascular risk in relation to total and regional adiposity is not known. We determined the strength of the associations between DXA- and conventional anthropometry determined fat distribution and T2D and CVD risk markers.Subjects/Methods:Waist (WC) and hip circumference (HC) and DXA was used to measure total and regional adiposity in 4950 (2119 men) participants aged 29–55 years from the Oxford Biobank without pre-existing T2D or CVD. Cross-sectional associations were compared between WC and HC vs. DXA-determined regional adiposity (all z-score normalised) with impaired fasting glucose, hypertriglyceridemia, hypertension and insulin resistance (IR).Results:Following adjustment for total adiposity, upper body adiposity measurements showed consistently increased risk of T2D and CVD risk markers except for abdominal subcutaneous fat in both sexes, and arm fat in men, which showed protective associations. Among upper adiposity depots, visceral fat mass showed stronger odds ratios (OR) ranging from 1.69 to 3.64 compared with WC 1.07–1.83. Among lower adiposity depots, HC showed modest protection for IR in both sexes (men: OR 0.80 (95% confidence interval 0.67, 0.96); women: 0.69 (0.56, 0.86)), whereas gynoid fat and in particular leg fat showed consistent and strong protective effects for all outcomes in both men and women. The differential effect of body fat distribution on CVD and T2D were more pronounced at higher levels of total adiposity.Conclusions:Compared with DXA, conventional anthropometry underestimates the associations of regional adiposity with T2D and CVD risk markers. After correcting for overall adiposity, greater subcutaneous fat mass in particular in the lower body is protective relative to greater android or visceral adipose tissue mass.

Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis: a translational cross-sectional study.

BackgroundStress hyperglycaemia (SHG) is a common complication in sepsis associated with poor outcome. Chemerin is an adipocytokine associated with inflammation and impaired glucose homeostasis in metabolic diseases such as type 2 diabetes (T2D). We aimed to investigate how alterations of circulating chemerin levels and corresponding visceral adipose tissue (VAT) expression are linked to glucose metabolism and prognosis in sepsis.MethodsClinical data and tissue samples were taken from a cross-sectional study including control, T2D and sepsis patients, all undergoing laparotomy. A second independent patient cohort of patients with sepsis was included to evaluate associations with prognosis. This was complemented by a murine model of peritoneal infection and a high-fat diet. We analysed circulating chemerin by enzyme-linked immunosorbent assay and VAT messenger RNA (mRNA) expression by real-time polymerase chain reaction.ResultsCirculating chemerin was increased in sepsis 1.69-fold compared with controls (p = 0.012) and 1.47-fold compared with T2D (p = 0.03). Otherwise, chemerin VAT mRNA expression was decreased in patients with sepsis (p = 0.006) and in septic diabetic animals (p = 0.009). Circulating chemerin correlated significantly with intra-operative glucose (r = 0.662; p = 0.01) and in trend with fasting glucose (r = 0.528; p = 0.052). After adjusting for body mass index or haemoglobin A1c, chemerin correlated in trend with insulin resistance evaluated using the logarithmised homeostasis model assessment of insulin resistance (r = 0.539, p = 0.071; r = 0.553, p = 0.062). Chemerin was positively associated with Acute Physiology and Chronic Health Evaluation II score in patients with sepsis (p = 0.036) and with clinical severity in septic mice (p = 0.031). In an independent study population, we confirmed association of chemerin with glucose levels in multivariate linear regression analysis (β = 0.556, p = 0.013). In patients with sepsis with SHG, non-survivors had significantly lower chemerin levels than survivors (0.38-fold, p = 0.006), while in patients without SHG, non-survivors had higher chemerin levels, not reaching significance (1.64-fold, p = 0.089). No difference was apparent in patients with pre-existing T2D (p = 0.44).ConclusionsWe show, for the first time to our knowledge, that chemerin is increased in sepsis and that it associates with impaired glucose metabolism and survival in these patients. It could be further evaluated as a biomarker to stratify mortality risk of patients with SHG.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1209-5) contains supplementary material, which is available to authorized users.

Pre-existing type 2 diabetes and risk of lung cancer: a report from two prospective cohort studies of 133 024 Chinese adults in urban Shanghai

ObjectivesObservational studies of type 2 diabetes (T2D) and lung cancer risk are limited and controversial. We thus examined the association between T2D and risk of incident lung cancer using a...

Diabetes Mellitus is Independently Associated with an Increased Risk of Mortality in Patients with Clear Cell Renal Cell Carcinoma

Conflicting data exist on the interaction of diabetes mellitus with outcomes in patients with renal cell carcinoma. We evaluated the association of diabetes mellitus with survival in patients with clear cell renal cell carcinoma treated with nephrectomy. We reviewed the records of 1,964 patients treated surgically for sporadic, unilateral, M0 clear cell renal cell carcinoma between 1990 and 2008. One pathologist re-reviewed all specimens to confirm clear cell renal cell carcinoma. We matched 257 patients with diabetes 1:2 to referent patients without diabetes according to clinicopathological and surgical features. Cancer specific and overall survival was estimated using the Kaplan-Meier method. Cox models were used to evaluate associations with outcomes. A total of 257 patients (13%) had diabetes mellitus. They were significantly older and more likely to be obese, and had higher Charlson scores, renal impairment and smoking rates, and worse performance status at surgery (p<0.001). Pathological features were similar between the groups. Median postoperative followup was 8.7 years. Five-year cancer specific survival was similar in patients with and without diabetes (82% vs 86%, p = 0.1) while 5-year overall survival was significantly worse in those with diabetes (65% vs 74%, p<0.001). On multivariable analysis diabetes mellitus independently predicted cancer specific mortality (HR 1.55, 95% CI 1.08-2.21, p = 0.02) and all-cause mortality (HR 1.32, 95% CI 1.06-1.64, p = 0.01). Our results suggest that diabetes mellitus is independently associated with decreased cancer specific and overall survival in patients with surgically treated clear cell renal cell carcinoma.

Pre-existing type-2 diabetes is not an adverse prognostic factor in patients with renal cell carcinoma: A single-center retrospective study

ObjectivesType-2 diabetes mellitus (DM) is a metabolic disease affecting several million people all over the world. The correlation between DM and malignancies is well established due to the findings of several large population-based studies. However, for endometrial, breast, colorectal, and liver cancers it has also been reported that DM could exert a negative impact on prognosis, causing a significant reduction in cancer-specific survival. A significant correlation with DM has also been demonstrated in renal cell carcinoma (RCC), but the possible prognostic role of DM in this setting has been poorly investigated and remains controversial. This study provides a retrospective analysis of a single-center surgical series with the aim of assessing the features and prognosis of RCC in DM patients. Materials and methodsSince 1987 a prospectively compiled database at our institute has collected the data of 1,761 patients who underwent surgery for RCC. All the patients are followed in a specially dedicated out-patient ambulatory. For this study, patients who were taking insulin or oral anti-hyperglycemic drugs before surgery for RCC were considered as DM cases. Their clinical and pathologic features were compared with those of patients without DM. Then, limiting the analysis to non-metastatic patients, the Kaplan-Meier method was used to calculate survival functions and univariable and multivariable Cox regression models addressed time to RCC-related and non RCC-related mortality. ResultsThe data of 1,604 patients without DM and 157 with DM (prevalence 8.9%) have been analyzed; the latter were more frequently males, older, and with higher co-morbidity and with more asymptomatic, smaller, and low stage neoplasms, though with a higher grading. After a median follow-up time of 53.4 months (IQR 20–97 months), the factors that influenced RCC-related mortality were the presence of symptoms at diagnosis, tumor size, TMN staging, and grading, while those that influenced non-RCC-related mortality were age, gender, and co-morbidities, whereas the presence of DM showed no influence at all. Moreover, in patients without and with DM, progression rate (19.8% vs. 15.1%, P = 0.195) and RCC-related mortality rate (9.6% vs. 5.3%, P = 0.102) were also statistically equivalent. ConclusionIn our experience, the prevalence of DM in RCC patients is close to 10%. Such a condition does not determine any significant influence on prognosis of RCC.

Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes

IntroductionGlucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes.MethodsEleven critically ill mechanically-ventilated patients with known type-2 diabetes received intravenous infusions of GLP-1 (1.2 pmol/kg/minute) and placebo from t = 0 to 270 minutes on separate days in randomised double-blind fashion. Between t = 30 to 270 minutes a liquid nutrient was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric catheter. Blood glucose, serum insulin and C-peptide, and plasma glucagon were measured. Data are mean ± SEM.ResultsGLP-1 attenuated the overall glycaemic response to nutrient (blood glucose AUC30-270 min: GLP-1 2,244 ± 184 vs. placebo 2,679 ± 233 mmol/l/minute; P = 0.02). Blood glucose was maintained at < 10 mmol/l in 6/11 patients when receiving GLP-1 and 4/11 with placebo. GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon.ConclusionsExogenous GLP-1 in a dose of 1.2 pmol/kg/minute attenuates the glycaemic response to small intestinal nutrient in critically ill patients with type-2 diabetes. Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group.Trial registrationANZCTR:ACTRN12610000185066