Background: This study reviews the mortality of patients with diabetic foot ulcers (DFU) from the first consultation with a Multidisciplinary Diabetic Foot Team (MDFT) and analyzes the main cause of death, as well as the relevant clinical factors associated with survival. Methods: Data of 338 consecutive patients referred to the MDFT center for a new DFU during the 2008–2014 period were analyzed. Follow-up: until death or until 30 April 2020, for up to 12.2 years. Results: Clinical characteristics: median age was 71 years, 92.9% had type 2 diabetes, and about 50% had micro-macrovascular complications. Ulcer characteristics: Wagner grade 1–2 (82.3%), ischemic (49.2%), and infected ulcers (56.2%). During follow-up, 201 patients died (59.5%), 110 (54.7%) due to cardiovascular disease. Kaplan—Meier curves estimated a reduction in survival of 60% with a 95% confidence interval (95% CI), (54.7–65.3) at 5 years. Cox regression analysis adjusted to a multivariate model showed the following associations with mortality, with hazard ratios (HRs) (95% CI): age, 1.07 (1.05–1.08); HbA1c value < 7% (53 mmol/mol), 1.43 (1.02–2.0); active smoking, 1.59 (1.02–2.47); ischemic heart or cerebrovascular disease, 1.55 (1.15–2.11); chronic kidney disease, 1.86 (1.37–2.53); and ulcer severity (SINBAD system) 1.12 (1.02–1.26). Conclusion: Patients with a history of DFU have high mortality. Two less known predictors of mortality were identified: HbA1c value < 7% (53 mmol/mol) and ulcer severity.

We analyzed the incidence of lower extremity amputations (LEAs) in the 3rd Health Care Area of Madrid before and after the March 2008 introduction of a multidisciplinary team for managing diabetic foot disease. We compared the amputation rates in people with and without diabetes during 2 periods: before (2001-2007) and after (2008-2011) the introduction of a Multidisciplinary Diabetic Foot Unit (MDFU). We also analyzed the trend of the amputation rates by joinpoint regression analysis and measured the annual percentage change (APC). During the study period, 514 nontraumatic LEAs were performed, 374 (73%) in people with diabetes and 140 (27%) in people without the disease. The incidence of LEAs showed a significant reduction in major amputations in people with diabetes, from 6.1 per 100 000 per year (95% confidence interval [CI] = 4.9 to 7.2), in the 2001 to 2007 period, to 4.0 per 100 000 per year (95% CI = 2.6 to 5.5) in the 2008 to 2011 period (P = .020). There were no changes in incidence of minor or total amputations in the diabetic population or in amputations in the nondiabetic population during the study period. Joinpoint regression analysis showed a significant reduction in the incidence of major LEAs in diabetic population with an APC of −6.6% (95% CI = −10.2 to −2.8; P = .003), but there were no other significant changes. This study demonstrates that the introduction of a multidisciplinary team, coordinated by an endocrinologist and a podiatrist, for managing diabetic foot disease is associated with a reduction in the incidence of major amputations in patients with diabetes.

The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin-linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycemia and insulinemia concurrently with a reduction of the expression and membrane presence of GLUT4 in the insulin-sensitive peripheral tissues compared with their wild-type littermates (WT). Tolerance tests and insulin sensitivity indexes confirmed the insulin resistance in cKD-ILK, suggesting a similar stage to prediabetes in humans. Under randomly fed conditions, no differences between cKD-ILK and WT were observed in the expression of insulin receptor (IR-B) and its substrate IRS-1 expressions. The IR-B isoform phosphorylated at tyrosines 1150/1151 was increased, but the AKT phosphorylation in serine 473 was reduced in cKD-ILK tissues. Similarly, ILK-blocked myotubes reduced their GLUT4 promoter activity and GLUT4 expression levels. On the other hand, the glucose uptake capacity in response to exogenous insulin was impaired when ILK was blockedin vivoandin vitro, although IR/IRS/AKT phosphorylation states were increased but not different between groups. We conclude that ILK depletion modifies the transcription of GLUT4, which results in reduced peripheral insulin sensitivity and glucose uptake, suggesting ILK as a molecular target and a prognostic biomarker of insulin resistance.