Key pointsr Adaptation to hypoxia makes the heart more oxygen efficient, by metabolising more glucose.In contrast, type 2 diabetes makes the heart metabolise more fatty acids.r Diabetes increases the chances of the heart being exposed to hypoxia, but whether the diabetic heart can adapt and respond is unknown.r In this study we show that diabetic hearts retain the ability to adapt their metabolism in response to hypoxia, with functional hypoxia signalling pathways.r However, the hypoxia-induced changes in metabolism are additive to abnormal baseline metabolism, resulting in hypoxic diabetic hearts metabolising more fat and less glucose than controls. This stops the diabetic heart being able to recover its function when stressed.r These results demonstrate that the diabetic heart retains metabolic flexibility to adapt to hypoxia, but is hindered by the baseline effects of the disease. This increases our understanding of how the diabetic heart is affected by hypoxia-associated complications of the disease.Abstract Hypoxia activates the hypoxia-inducible factor (HIF), promoting glycolysis and suppressing mitochondrial respiration. In the type 2 diabetic heart, glycolysis is suppressed whereas fatty acid metabolism is promoted. The diabetic heart experiences chronic hypoxia as a consequence of increased obstructive sleep apnoea and cardiovascular disease. Given the opposing metabolic effects of hypoxia and diabetes, we questioned whether diabetes affects cardiac metabolic adaptation to hypoxia. Control and type 2 diabetic rats were housed for 3 weeks in normoxia or 11% oxygen. Metabolism and function were measured in the isolated perfused heart using radiolabelled substrates. Following chronic hypoxia, both control and diabetic hearts upregulated glycolysis, lactate efflux and glycogen content and decreased fatty acid oxidation rates, with similar activation of HIF signalling pathways. However, hypoxia-induced changes were superimposed on diabetic hearts that were metabolically abnormal in normoxia, resulting in glycolytic rates 30% lower, and fatty acid oxidation 36% higher, in hypoxic diabetic hearts than hypoxic controls. Peroxisome proliferator-activated receptor α target proteins were suppressed by hypoxia, but activated by diabetes. Mitochondrial respiration in diabetic hearts was divergently activated following hypoxia compared with controls. These differences in metabolism were associated with decreased contractile recovery of the hypoxic diabetic heart following an acute hypoxic insult. In conclusion, type 2 diabetic hearts retain metabolic flexibility to adapt to hypoxia, with normal HIF signalling pathways. However, they are more dependent on oxidative metabolism following hypoxia due to abnormal normoxic metabolism, which was associated with a functional deficit in response to stress.
Background and Aims: The India Microalbuminuria Survey (IMS) was a cross-sectional, national survey to understand the prevalence of microalbuminuria (MAU) in Indian hypertensive patients. In the IMS study, 992 patients out of 1369 were diabetic. The objectives of this subset analysis were to estimate the prevalence of microalbuminuria in Indian hypertensives patients with concomitant T2DM. Methods: This cross-sectional subset analysis included 992 diabetic patients visiting a physician’s clinic, from 121 centres across India. Inclusion criteria were male and female outpatients aged ≥ 18years with hypertension and concomitant type II DM and no reason for false positive microalbuminuria reflected in dipstick tests. Exclusion criteria were presence of secondary hypertension and existing CKD. Microalbuminuria was diagnosed if the urinary albumin excretion was more than 30 mg/L using the ACR Kit manufactured by Biosense Technologies Pvt. Ltd. Patient data was analyzed with the help of the SPSS software. Results: The mean age of the patients was 54.04 years. There were 186 (18.75 %) patients below 45 years of age and 806 (81.25%) patients more than 45 years of age. The prevalence of microalbuminuria in hypertensive patients with concomitant type II DM was 31.04 %. The prevalence was 34.4% in patients below 45 years of and 30.27% in patients above 45 years age. Conclusions: This study reports a high prevalence of microalbuminuria in Indian patients with hypertension and concomitant type II DM. Hence, early recognition of renal dysfunction through detection of microalbuminuria and to start treatment without any delay will confer future protection from end stage renal disease as well as hypertension and its complications in type 2 diabetic patients. Disclosure B.Saboo: None. K.Mehta: Employee; JB Chemicals and Pharmaceuticals Ltd. A.Naik: Employee; JB Chemicals and Pharmaceuticals Ltd.
Aims Cardiovascular disease is the leading cause of mortality in people with type 2 diabetes. Following a myocardial infarction, the heart must adapt to the decreased oxygen availability by switching to more oxygen-efficient metabolism. We hypothesise that adaptation to hypoxia is impaired in type 2 diabetes.
Anastomotic leaks are among the most dreaded complications after intestinal surgeries. Some leaks presents in a dramatic fashion early in the postoperative period, leaving little doubt about the diagnosis. However, many others present in a far more subtle fashion, often relatively late in the postoperative period, and can be difficult to distinguish from other postoperative infectious complications. We report a case of a 66 year old male who presented with bleeding per rectum since 3-4 months. He had a history of being operated for hemorrhoidectomy 9 years ago. He underwent a colonoscopy which detected a large sessile polyp at the rectosigmoid junction for which polypectomy was done. The histopathology of the polyp revealed moderately differentiated adenocarcinoma arising within the villoglandular polyp (malignant polyp) with base involved. He was then operated for anterior resection followed by colorectal anastomosis. Until postoperative day 5, the patient had no symptoms and signs of having an anastomotic leak, after which he complained of extreme abdominal discomfort, sudden distension and the drain had collected 35ml of feculent matter. It is a rare and poorly understood case of anastomotic leak presenting without high fever, tachycardia, a rigid abdomen and hemodynamic instability.
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