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.

Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening.

OBJECTIVE: Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis. RESULTS: The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI). CONCLUSIONS: Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.

Benign prostatic hyperplasia: when to 'watch and wait,' when and how to treat.

Benign prostatic hyperplasia (BPH) is a clinical diagnosis. While BPH is a common cause of lower urinary tract symptoms (LUTS) in men, LUTS can signify a number of other disease states. For this reason, the patient evaluation, which includes a digital rectal examination, and careful differential diagnosis are crucial in men with LUTS. Many men with BPH are asymptomatic, and many others are not bothered by their symptoms; watchful waiting is appropriate management for these patients. When symptoms affect quality of life, pharmacologic therapy should be an option; choices include an alphablocker, a 5 alpha-reductase inhibitor, or, for men with larger prostates, a combination of the two. Surgical intervention is indicated when BPH leads to other medical complications, including urinary retention and renal insufficiency.

Addressing Hospital Readmissions: Impact of Weekly Review.

BACKGROUND AND OBJECTIVES: The prevention of hospital readmissions has become an area for improvement for most health care organizations. Systematic reviews have been unable to identify a single intervention or bundle of interventions that reliably reduced risk of readmission in a generalizable manner. The aim of this quality improvement project was to examine the readmission rate to a family medicine residency program inpatient service following the implementation of a once per week session that reviewed patients who were readmitted during the prior week. METHODS: The inpatient admissions and readmission to the family medicine inpatient service associated with a large academic health center were used for analysis. The impact of a regularly scheduled multidisciplinary team meeting that reviewed a list of patients was examined. Readmitted patients who were at high risk for readmission were specifically identified. Descriptive statistics were used to characterize and summarize the integral data obtained. The weekly readmission rate was presented using a control chart. RESULTS: The readmission rate for the patients hospitalized after the intervention was 18.4%, compared to the readmission rate prior to the intervention (23.0%). While not a statistically different rate, a significant signal was noted. Demographic differences were noted in the group of patients considered to be high risk for readmission. CONCLUSIONS: Regular rounds of an inpatient team that focuses on readmissions during the previous week reduced hospital readmissions. The impact of these sessions appears to be multifactorial.

Chronic pelvic pain in women: evaluation and management in primary care.

Chronic pelvic pain (CPP) in women is a common disorder, affecting as many as 15% of adult women, and often provides both a diagnostic and therapeutic challenge. Pain in CPP may originate directly from pelvic organs, or may be referred from more distant tissue sites. A comprehensive medical history and physical examination should include special attention to gynecological, urological, gastrointestinal, psychiatric, myofascial, and neuromuscular systems. The effective management of CPP may involve comprehensive evaluations by specialists, psychologists, and multiple office visits. Physicians should address CPP as a chronic disease. Combining lifestyle modification with other traditional treatments produces better outcomes. Laboratory tests, transvaginal ultrasound, and laparoscopy may identify serious disease or provide significant reassurance to patient. Specific surgical procedures for various conditions and pain relief measures are beneficial in selected patients. A sensitive physician who is willing to spend adequate time and coordinate care with specialists can markedly diminish the suffering of these patients.

Polycystic ovary syndrome [PCOS]: comprehensive management in primary care.

Polycystic ovary syndrome is a common premenopausal endocrino-metabolic disorder. In addition to hyperandrogenism, menstrual abnormalities, ovulatory disturbances and infertility, insulin resistance, dyslipidemia, and obesity may eventuate in long-term cardiovascular consequences.

Acute pelvic pain: evaluation and management.

Acute pelvic pain in women is often a diagnostic dilemma. Obstetrical, gynecological, urological or gastrointestinal causes must be considered. Stabilization, immediate therapy and early consultation are often indicated. If no etiology is found, conservative management with frequent re-evaluation is adequate.

Nonsteroidal anti-inflammatory drugs in the treatment of low back pain.

Low back pain (LBP) is amongst the top ten most common conditions presenting to primary care clinicians in the ambulatory setting. Further, it accounts for a significant amount of health care expenditure; indeed, over one third of all disability dollars spent in the United States is attributable to low back pain. In most cases, acute low back pain is a self-limiting disease. There are many evidence-based guidelines for the management of LBP. The most common risk factor for development of LBP is previous LBP, heavy physical work, and psychosocial risk factors. Management of LBP includes identification of red flags, exclusion of specific secondary causes, and comprehensive musculoskeletal/neurological examination of the lower extremities. In uncomplicated LBP, imaging is unnecessary unless symptoms become protracted. Reassurance that LBP will likely resolve and advice to maintain an active lifestyle despite LBP are the cornerstones of management. Medications are provided not because they change the natural history of the disorder, but rather because they enhance the ability of the patient to become more active, and in some cases, to sleep better. The most commonly prescribed medications include nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants. Although NSAIDs are a chemically diverse class, their similarities, efficacy, tolerability, and adverse effect profile have more similarities than differences. The most common side effects of NSAIDs are gastrointestinal. Agents with cyclo-oxygenase 2 selectivity are associated with reduced gastrointestinal bleeding, but problematic increases in adverse cardiovascular outcomes continue to spark concern. Fortunately, short-term use of NSAIDs for LBP is generally both safe and effective. This review will focus on the role of NSAIDs in the management of LBP.

Enhanced glycemic control with combination therapy for type 2 diabetes in primary care.

Type 2 diabetes mellitus is an increasingly common medical problem for primary care clinicians to address. Treatment of diabetes has evolved from simple replacement of insulin (directly or through insulin secretagogs) through capture of mechanisms such as insulin sensitizers, alpha-glucosidase inhibitors, and incretins. Only very recently has recognition of the critical role of the gastrointestinal system as a major culprit in glucose dysregulation been established. Since glycated hemoglobin A(1c) reductions provide meaningful risk reduction as well as improved quality of life, it is worthwhile to explore evolving paths for more efficient use of the currently available pharmacotherapies. Because diabetes is a progressive disease, even transiently successful treatment will likely require augmentation as the disorder progresses. Pharmacotherapies with complementary mechanisms of action will be necessary to achieve glycemic goals. Hence, clinicians need to be well informed about the various noninsulin alternatives that have been shown to be successful in glycemic goal attainment. This article reviews the benefits of glucose control, the current status of diabetes control, pertinent pathophysiology, available pharmacological classes for combination, limitations of current therapies, and suggestions for appropriate combination therapies, including specific suggestions for thresholds at which different strategies might be most effectively utilized by primary care clinicians.