[ Diabetes Solutions ]

Triglycerides and Amputation Risk in Patients With Diabetes: Ten-year follow-up in the DISTANCE study

Obesity is associated with leptin resistance as evidenced by hyperleptinemia. Serum lipIds were measured at baseline (total and HDL-cholesterol, triglycerIdes and calculated LDL-cholesterol, Lipoprotein (a)). In nonketotic diabetic rats untreated with insulin, myocardial triglycerides repeatedly increased and declined to control levels. Insulin resistance impairs VLDL particle clearance, leading to greater interchange of core triglyceride from VLDL with LDL and HDL, with LDL and HDL triglyceride enrichment leading both to become substrates for hepatic lipase, resulting in smaller, denser particles. RESULTS— In the multiple regression analysis, LDL cholesterol (positively) and triglycerides (negatively) were independently related to the Lp(a) concentration, and they explained the 6.6 and 7.8% of the Lp(a) variation, respectively. Shulman’s group in the Cellular and Molecular Physiology department at Yale University School of Medicine’s Howard Hughes Medical Institute. The formation of fat happens between meals or overnight when insulin levels are low.

Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. However, this modest collinearity was not considered sufficient to distort our triglyceride effect estimates from the Cox regression models. No significant change in or total or HDL cholesterol, HbA1c, fasting glucose, fasting insulin or body weight was observed. Fat cells have a tremendous storage capacity, which may contribute to obesity. “These results provide new insights into the pathogenesis of non-alcoholic liver disease and provides new approaches to treat fatty liver disease, which is now the most common liver disease in the world,” said Shulman. This is in contrast to low HDL, which was not associated with increased amputation risk. The threshold of LDL levels above 160 mg/dL was also associated with increased risk of amputation.

Combination therapy with a fibrate should follow if needed. Our results suggest that high triglyceride levels, independent of the other major lipid components, may put patients at risk for one major diabetes complication—LEA. These results do not favour a role of human APOA5 in lipoprotein lipase-mediated lipolysis. These results add to the finding in prior studies that elevated triglyceride levels may be a risk factor for complications of diabetes (5,7,8), including LEA (9,10). However, the current study involved a larger population and found the association to be statistically significant even after adjusting the models for a multitude of variables that were not assessed in the prior studies. Given the current state of the literature, the guidelines on triglyceride management do not advocate aggressive treatment. Melander, V.


Clearly, further studies are needed to ascertain the role of hypertriglyceridemia in these diabetic sequelae. Our study gives further support to the notion that triglycerides may be one of the key modifiable risk factors in the development of amputations. If this association holds in clinical trials, then clinicians may have a target with the potential to improve important patient outcomes. If the Nuvaring was what was elevating my triglycerides is it possible they will go back to normal and how long after being off them should there start to be a difference? However, our sensitivity analysis using missing triglycerides as an indicator and evaluating the entire diabetes cohort suggests that missing data did not substantially bias our findings. Once digested, triglycerides circulate in the bloodstream to be used as energy by the cells. In our study, the longitudinal study design and exclusion of patients with prevalent amputations at baseline precludes time-ordering violations (i.e., LEA preceding the triglyceride ascertainment).

For more information about triglycerides, visit webmd.com/triglycerides. Overweight women with PCOS may also have low levels of HDL cholesterol and high levels of triglycerides. Your health care providers may check you for other risk factors for heart disease, such as high blood pressure, high blood glucose, and too much fat around your waist. In summary, elevated triglyceride level was associated with subsequent LEA independently of the other lipid components and a wide range of potential confounders in this large, well-characterized diabetic cohort. Though specific guidelines exist for cholesterol (LDL and HDL levels) management in this patient population, only vague guidelines exist for triglyceride management (23). This observational study suggests that triglyceride levels are predictive of amputation risk in a stepwise fashion. Recent studies show this cut off point for deciding on treatment may lead to exclusion of some patients at risk from CHD.

More research is necessary to define a causal role of triglyceride levels on amputation risk in diabetic patients. Based on this current robust cohort study, such research should be a priority. B.C.C. Limit high-calorie foods and carbohydrate, especially high-sugar foods such as cookies, soda, and fruit juices. E.F. proposed the hypothesis and helped with the manuscript. J.L.

performed the statistical analysis. K.K. helped with statistical interpretation and contributed to the manuscript. R.P.-B. contributed to the manuscript. H.M. reviewed the manuscript.

A.J.K. was integrally involved in the creation of the cohort and was significantly involved in analysis and writing the manuscript.

Tags: , ,