Adipose Tissue Insulin Resistance Predicts the Severity of Liver Fibrosis in Patients With Type 2 Diabetes and NAFLD.

CONTEXT: Although type 2 diabetes (T2D) is a risk factor for liver fibrosis in nonalcoholic fatty liver disease (NAFLD), the specific contribution of insulin resistance (IR) relative to other factors is unknown. OBJECTIVE: Assess the impact on liver fibrosis in NAFLD of adipose tissue (adipose tissue insulin resistance index [adipo-IR]) and liver (Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]) IR in people with T2D and NAFLD. DESIGN: Participants were screened by elastography in the outpatient clinics for hepatic steatosis and fibrosis, including routine metabolites, cytokeratin-18 (a marker of hepatocyte apoptosis/steatohepatitis), and HOMA-IR/adipo-IR. SETTING: University ambulatory care practice. PARTICIPANTS: A total of 483 participants with T2D. INTERVENTION: Screening for steatosis and fibrosis with elastography. MAIN OUTCOME MEASURES: Liver steatosis (controlled attenuation parameter), fibrosis (liver stiffness measurement), and measurements of IR (adipo-IR, HOMA-IR) and fibrosis (cytokeratin-18). RESULTS: Clinically significant liver fibrosis (stage F ≥ 2 = liver stiffness measurement ≥8.0 kPa) was found in 11%, having more features of the metabolic syndrome, lower adiponectin, and higher aspartate aminotransferase (AST), alanine aminotransferase, liver fat, and cytokeratin-18 (P < 0.05-0.01). In multivariable analysis including just clinical variables (model 1), obesity (body mass index [BMI]) had the strongest association with fibrosis (odds ratio, 2.56; CI, 1.87-3.50; P < 0.01). When metabolic measurements and cytokeratin-18 were included (model 2), only BMI, AST, and liver fat remained significant. When fibrosis stage was adjusted for BMI, AST, and steatosis (model 3), only Adipo-IR remained strongly associated with fibrosis (OR, 1.51; CI, 1.05-2.16; P = 0.03), but not BMI, hepatic IR, or steatosis. CONCLUSIONS: These findings pinpoint to the central role of dysfunctional, insulin-resistant adipose tissue to advanced fibrosis in T2D, beyond simply BMI or steatosis. The clinical implication is that targeting adipose tissue should be the priority of treatment in NAFLD.

Venous Ulcers: Diagnosis and Treatment.

Venous ulcers are the most common type of chronic lower extremity ulcers, affecting 1% to 3% of the U.S. population. Venous hypertension as a result of venous reflux (incompetence) or obstruction is thought to be the primary underlying mechanism for venous ulcer formation. Risk factors for the development of venous ulcers include age 55 years or older, family history of chronic venous insufficiency, higher body mass index, history of pulmonary embolism or superficial/deep venous thrombosis, lower extremity skeletal or joint disease, higher number of pregnancies, parental history of ankle ulcers, physical inactivity, history of ulcers, severe lipodermatosclerosis, and venous reflux in deep veins. Poor prognostic signs for healing include ulcer duration longer than three months, initial ulcer length of 10 cm or more, presence of lower limb arterial disease, advanced age, and elevated body mass index. On physical examination, venous ulcers are generally irregular and shallow with well-defined borders and are often located over bony prominences. Signs of venous disease, such as varicose veins, edema, or venous dermatitis, may be present. Other associated findings include telangiectasias, corona phlebectatica, atrophie blanche, lipodermatosclerosis, and inverted champagne-bottle deformity of the lower leg. Chronic venous ulcers significantly impact quality of life. Severe complications include infection and malignant change. Current evidence supports treatment of venous ulcers with compression therapy, exercise, dressings, pentoxifylline, and tissue products. Referral to a wound subspecialist should be considered for ulcers that are large, of prolonged duration, or refractory to conservative measures. Early venous ablation and surgical intervention to correct superficial venous reflux can improve healing and decrease recurrence rates.