Comparison of single and dual latent tuberculosis screening strategies before biologic and targeted therapy in patients with rheumatic diseases: a retrospective cohort study.

PURPOSE: Before biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) treatment, latent tuberculosis infection (LTBI) screening by tuberculin skin test (TST) or interferon gamma release assay (IGRA) is recommended. However, both tests have reduced reliability in immunosuppressed patients. We investigated whether dual LTBI screening with both tests could reduce the incidence of tuberculosis. METHODS: Consecutive patients receiving b/tsDMARDs for rheumatic diseases in a regional hospital were recruited. All patients underwent either TST/IGRA or both. They were categorised into a single or dual testing group and were followed up for at least 6 months. Isoniazid was prescribed if any one test was positive. RESULTS: In total, 217 patients were included in this study; 121 underwent single LTBI testing and 96 underwent dual testing. Tuberculosis occurred in nine patients in the single testing group and one patient in the dual testing group (7.4% vs 1.0%, P=0.045). However, the difference was not statistically significant when follow-up duration was considered (log rank test). In total, 71 patients tested positive for LTBI with isoniazid treatment (28.9% in the single testing group and 45.8% in the dual testing group, P=0.007). Agreement between the IGRA and TST was 74.4% (Cohen's kappa=0.413); agreement was lower in patients receiving prednisolone. Infliximab use was independently associated with tuberculosis (P=0.032). Mild isoniazid-related side-effects occurred in seven patients. CONCLUSIONS: Dual LTBI testing with both TST and IGRA is effective and safe. It might be useful for patients receiving prednisolone at the time of LTBI screening, or if infliximab therapy is anticipated.

Skiing and snowboarding head injury: A retrospective centre-based study and implications for helmet test standards.

BACKGROUND: Head injury occurs in up to 47% of skiing or snowboarding injuries and is the predominant cause of death in these sports. In most existing literature reporting injury type and prevalence, head injury mechanisms are underreported. Thus, protective equipment design relies on safety evaluation test protocols that are likely oversimplified. This study aims to characterize severity and mechanism of head injuries suffered while skiing and snowboarding in a form appropriate to supplement existing helmet evaluation methods. METHODS: A 6-year, multicentre, retrospective clinical record review used emergency databases from two major trauma centres and Coroner's reports to identify relevant cases which indicated head impact. Records were investigated to understand the relationships between helmet use, injury type and severity, and injury mechanism. Descriptive statistics and odds ratios aided interpretation of the data. FINDINGS: The snow sport head injury database included 766 cases. "Simple fall", "jump impact" and "impact with object" were the most common injury mechanisms while concussion was observed to be the most common injury type. Compared to "edge catch", moderate or serious head injury was more common for "fall from height" (OR = 4.69; 95% CI = 1.44-16.23; P = 0.05), "jump impact" (OR = 3.18; 95% CI = 1.48-7.26; P = 0.01) and "impact with object" (OR = 2.44; 95% CI = 1.14-5.56; P = 0.05). Occipital head impact was associated with increased odds of concussion (OR = 7.46; 95% CI = 4.55-12.56; P = 0.001). INTERPRETATION: Snow sport head injury mechanisms are complex and cannot be represented through a single impact scenario. By relating clinical data to injury mechanism, improved evaluation methods for protective measures and ultimately better protection can be achieved.

Comparison of a commercial interferon-gamma release assay and tuberculin skin test for the detection of latent tuberculosis infection in Hong Kong arthritis patients who are candidates for biologic agents.

INTRODUCTION: It is universally agreed that screening for latent tuberculosis infection prior to biologic therapy is necessary, especially in endemic areas such as Hong Kong. There are still, however, controversies regarding how best to accomplish this task. The tuberculin skin test has been the routine screening tool for latent tuberculosis infection in Hong Kong for the past decade although accuracy is far from perfect, especially in patients who have been vaccinated with Bacillus Calmette-Guérin, who are immunocompromised, or who have atypical mycobacterium infection. The new interferon-gamma release assays have been shown to improve specificity and probably sensitivity. This study aimed to evaluate agreement between the interferon-gamma release assay and the tuberculin skin test in the diagnosis of latent tuberculosis infection in patients with arthritic diseases scheduled to receive biologic agents. METHODS: We reviewed 38 patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis at a local hospital in Hong Kong from August 2013 to April 2014. They were all considered candidates for biologic agents. The patients underwent both the interferon-gamma release assay (ASACIR.TB; A.TB) and the tuberculin skin test simultaneously. Concurrent medications were documented. Patients who tested positive for either test (ie A.TB+ or TST+) were prescribed treatment for latent tuberculosis if they were to be given biologic agents. All patients were followed up regularly for 1 year and the development of active tuberculosis infection was evaluated. RESULTS: Based on an induration of 10 mm in diameter as the cut-off value, 13 (34.2%) of 38 patients had a positive tuberculin skin test. Of the 38 patients, 11 (28.9%) also had a positive interferon-gamma release assay. The agreement between interferon-gamma release assay and tuberculin skin test was 73.7% (kappa=0.39). Six patients were TST+/A.TB- and four were TST-/A.TB+. When positive tuberculin skin test was defined as an induration of 5-mm diameter, the agreement between the two tests improved with a kappa value of 0.47. In that case, half of the patients had a positive tuberculin skin test; among them, nine were TST+/A.TB-. Only one was TST-/A.TB+. Subgroup analysis showed that the agreement between both tests improved further (kappa=0.69) in patients not taking a concurrent systemic steroid. For patients prescribed systemic steroid, the agreement was only slight with a kappa value of 0.066. Finally, none of the 38 patients, of whom 32 had an exposure to biologic agents, developed active tuberculosis during the 1-year follow-up period. CONCLUSION: In a tuberculosis-endemic population, although 10-mm diameter induration is the usual cut-off for a positive tuberculin skin test, the level of agreement between the interferon-gamma release assay and tuberculin skin test improved from fair to moderate when the cut-off was lowered to 5 mm. A dual testing strategy of tuberculin skin test and interferon-gamma release assays appeared to be effective and should be pursued especially in patients who are on systemic steroid therapy. Nonetheless, the issue of potential overtreatment is yet to be evaluated.

Oyster-associated outbreaks of Norovirus gastroenteritis in Singapore.

Outbreaks of gastroenteritis associated with the consumption of raw imported half-shelled frozen oysters occurred in Singapore between 16 Dec 2003 and 04 Jan 2004. A total of 305 cases were reported with clinical symptoms of diarrhoea (94%), abdominal cramps (72%), vomiting (69%) and fever (54%). The median incubation period was 30.8h and the duration of illness was 2-3 days. The overall relative risk of oyster consumption was 14.1 (95% CI: 8.3-24.0, P<0.001). Stool and oyster samples tested negative for common bacterial pathogens, including Vibrio parahaemolyticus. However, stool samples were positive for the presence of Norovirus group II RNA via RT PCR while oyster samples indicated the presence of Norovirus particles by electron microscopy. The clinical and epidemiological features were suggestive of Norovirus gastroenteritis and were subsequently confirmed by laboratory tests of stools and implicated oysters. Steps have been taken to ensure that food outlets do not thaw frozen oysters and serve them raw.

Differential decline in tuberculosis incidence among US- and non-US-born persons in New York City.

SETTING: A large urban tuberculosis control program. OBJECTIVES: To examine changes in tuberculosis incidence and characteristics of cases in New York City (NYC), and assess the epidemiology of tuberculosis among non-US-born persons. DESIGN: Tuberculosis surveillance data (1995-1999) for NYC were analyzed. RESULTS: Tuberculosis incidence decreased by 56.6% in US-born and 19.6% in non-US-born persons (age-adjusted) over the study period. The decline in tuberculosis incidence among US-born persons was more substantial in the first half of the study period (23-24%) than in the second half (13-15%). The greatest decline in incidence was among US-born Hispanic or Black males aged 25-64. However, although there was an overall decline in incidence among non-US-born persons, there was no significant change in any sex or racial/ethnic subgroup. The percent of multidrug-resistant (MDR) cases among non-US-born patients remained stable, but recent arrivals accounted for 79% of non-US-born MDR-TB patients in 1999, a significant increase from 16% in 1997. CONCLUSIONS: Continuing current tuberculosis control efforts and treatment of immigrants with latent tuberculosis infection are of highest priority for reducing incident cases in NYC. Global collaboration towards earlier detection and treatment of active tuberculosis cases in high incidence countries is also essential.

Socio-economic status and puberty are the main factors determining anaemia in adolescent girls and boys in East Java, Indonesia.

OBJECTIVE: To determine prevalence and contributing factors of anaemia in adolescents. DESIGN: Cross-sectional study of anaemia prevalence, socio-economic status and puberty. SETTING: Schools in East Java, Indonesia. SUBJECTS: Male and female adolescent pupils (age 12-15 y; n=6486). RESULTS: Anaemia prevalence was 25.8% among girls (n=3486), 24.5% among pre-pubertal boys (n=821), and 12.1% among pubertal boys (n=2179). Socio-economic status, indicated by type of school attended, was an important factor determining the risk of anaemia. Girls had a higher risk when they attended a poor school (OR poorest school, 1.00; other schools, 0.67-0.87), had reached puberty (OR, 1.25), had lower retinol intake (OR 1st-4th quartiles-1.00, 0.97, 0.89, 0.77) and higher vitamin A intake from plant sources (OR 1st-4th quartiles-1.00, 1.10, 1.31, 1.04). Boys had a higher risk of anaemia when they attended a poor school (OR poorest school 1.00, other schools 0.54-0.63), were younger (OR per year=0.79), had not yet reached puberty (OR not yet, 1.00; already, 0.78), were shorter (OR per cm 0.95), had smaller mid-upper-arm circumference (MUAC) (OR per mm 0.99) and lower retinol intake (OR 1st-4th quartile 1.00, 0.67, 0.74, 0.68). CONCLUSIONS: Anaemia in adolescents should be reported separately for pre-pubertal and pubertal subjects and for different ages, and the population's socio-economic status should be specified. The results of this survey call for treatment of anaemia in adolescents. Given Indonesia's current situation, micronutrient intake of adolescents should be increased using supplements for all girls and for pre-pubertal boys. SPONSORSHIP: This survey was funded by USAID through the OMNI project.

Better use of data to define nutrition priority and action.

Nutrition and dietary survey data has been useful in defining the magnitude of malnutrition and dietary deficit. Such information has been helpful in gaining attention to support or to do more to improve nutrition-advocacy. However, there are also greater opportunities to use the common data to guide the program action. In summary, we have plenty of good nutrition and dietary information available to us in the planning and operation of nutrition intervention program. If we go beyond the use of data to justify area or subject of engagement, we can also use the same data for more efficient and more effective program without additional cost to us.

Uncommon hand tumours.

This paper presented clinical examples of some rare or uncommon presentations of tumours of the hand, including glomus tumour, intraosseous dermoid, fibrolipoma of the radial nerve, blastomycotic cyst and synovial sarcoma. Each lesion is illustrated by review of case histories, radiological and pathological features.

Intrathecal morphine for postpartum tubal ligation postoperative analgesia.

UNLABELLED: Intrathecal morphine (ITM) provides effective postoperative cesarean delivery analgesia but has not been reported for postoperative postpartum tubal ligation (PPTL) analgesia. We designed this prospective, randomized, double-blinded study to determine the efficacy of 100 microg ITM for postoperative PPTL analgesia. Sixty-six women received spinal anesthesia with 60 mg (1.2 mL) of 5% hyperbaric lidocaine, 10 microg (0.2 mL) of fentanyl, and either 0.2 mL of 0.9% saline (normal saline; NS) or 100 microg (0.2 mL) of morphine (morphine sulfate, MS). Postoperative analgesia was limited to patient-controlled IV analgesia morphine. Six women (three NS and three MS) were excluded because of major protocol violations. Twenty-four-hour patient-controlled IV analgesia morphine use was (mean +/- SD) 39.6 +/- 19.6 mg in the NS group and 1.1 +/- 2.5 mg in the MS group (P < 0.0000001). Visual analog scale scores for crampy and incisional pain (rest and movement) were significantly higher in the NS group compared with the MS group at 4, 8, 12, and 24 h (P < 0.001). The adverse effect profile was similar between groups. Visual analog scale satisfaction scores (mean +/- SD) were 96.6 +/- 16.0 in the MS group and 84.2 +/- 23.6 in NS group (P < 0.05). The results of this study indicate that women experience significant postoperative pain after PPTL surgery, and this pain is effectively obviated by 100 microg ITM. IMPLICATIONS: This investigation documents the extent of the significant postoperative pain experienced by women after routine postpartum tubal ligation surgery and demonstrates the efficacy of a small dose (100 microg) of intrathecal morphine to obviate this pain with minimal adverse effects.

Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice.

The d, ash, and ln coat color mutations provide a unique model system for the study of vesicle transport in mammals. All three mutant loci encode genes that are required for the polarized transport of melanosomes, the specialized, pigment-containing organelles of melanocytes, to the neighboring keratinocytes and eventually into coat hairs. Genetic studies suggest that these genes function in the same or overlapping pathways and are supported by biochemical studies showing that d encodes an actin-based melanosome transport motor, MyoVa, whereas ash encodes Rab27a, a protein that localizes to the melanosome and is postulated to serve as the MyoVa receptor. Here we show that ln encodes melanophilin (Mlph), a previously undescribed protein with homology to Rab effectors such as granuphilin, Slp3-a, and rabphilin-3A. Like all of these effectors, Mlph possesses two Zn(2+)-binding CX(2)CX(13,14)CX(2)C motifs and a short aromatic-rich amino acid region that is critical for Rab binding. However, Mlph does not contain the two Ca(2+)-binding C(2) domains found in these and other proteins involved in vesicle transport, suggesting that it represents a previously unrecognized class of Rab effectors. Collectively, our data show that Mlph is a critical component of the melanosome transport machinery and suggest that Mlph might function as part of a transport complex with Rab27a and MyoVa.

Estimating the prevalence of anaemia: a comparison of three methods.

OBJECTIVE: To determine the most effective method for analysing haemoglobin concentrations in large surveys in remote areas, and to compare two methods (indirect cyanmethaemoglobin and HemoCue) with the conventional method (direct cyanmethaemoglobin). METHODS: Samples of venous and capillary blood from 121 mothers in Indonesia were compared using all three methods. FINDINGS: When the indirect cyanmethaemoglobin method was used the prevalence of anaemia was 31-38%. When the direct cyanmethaemoglobin or HemoCue method was used the prevalence was 14-18%. Indirect measurement of cyanmethaemoglobin had the highest coefficient of variation and the largest standard deviation of the difference between the first and second assessment of the same blood sample (10-12 g/l indirect measurement vs 4 g/l direct measurement). In comparison with direct cyanmethaemoglobin measurement of venous blood, HemoCue had the highest sensitivity (82.4%) and specificity (94.2%) when used for venous blood. CONCLUSIONS: Where field conditions and local resources allow it, haemoglobin concentration should be assessed with the direct cyanmethaemoglobin method, the gold standard. However, the HemoCue method can be used for surveys involving different laboratories or which are conducted in relatively remote areas. In very hot and humid climates, HemoCue microcuvettes should be discarded if not used within a few days of opening the container containing the cuvettes.

Continuation of the decline in prevalence of anemia in low-income infants and children in five states.

OBJECTIVE: To examine whether there is a continuation of the decline in prevalence of anemia among low-income infants and children 6.0 to 59.9 months old from the early 1980s to the mid-1990s. STUDY DESIGN: Cross-sectional trend analysis of data from the Centers for Disease Control and Prevention's Pediatric Nutrition Surveillance System from the 5 states (Colorado, New Mexico, Oklahoma, Utah, and Vermont) that have been using the same laboratory method for anemia screening since 1984 or earlier. RESULTS: The overall prevalence of anemia decreased substantially in each state from the early 1980s to the mid-1990s as follows: Colorado by 52%; New Mexico by 75%; Oklahoma by 67%; Utah by 57%; and Vermont by 48%. In each state, the prevalence of anemia declined for children of different age groups, birth weights, genders, type of pediatric care visit (screening or follow-up), and most race/ethnic groups. CONCLUSIONS: The decline in the prevalence of anemia initially observed in the 1980s continued well into the 1990s. This decline is likely attributable to better iron nutrition related to greater usage of iron-fortified products and possibly better iron bioavailability in some of the food products.

Coarctation co-existing with tetralogy of Fallot and pulmonary atresia.

We describe the finding of unsuspected aortic coarctation, discovered by catheterisation at 4 months, in a neonate first daignosed on the fourth day of life as having tetralogy of Fallot with pulmonary atresia and major aorto-to-pulmonary collateral arteries. This previously unreported combination contravenes the established theory of patterns of flow during fetal life, and presented difficult issues in clinical management.

High and low hemoglobin levels during pregnancy: differential risks for preterm birth and small for gestational age.

OBJECTIVE: To examine the association of maternal hemoglobin during pregnancy with preterm birth and small for gestational age (SGA). METHODS: We performed a retrospective cohort analysis of hemoglobin and birth outcome among 173,031 pregnant women who attended publicly funded health programs in ten states and delivered a liveborn infant at 26-42 weeks' gestation. We defined preterm as less than 37 weeks' gestation and SGA as less than the tenth percentile of a US fetal growth reference. RESULTS: Risk of preterm birth was increased in women with low hemoglobin level in the first and second trimester. The odds ratio (OR) for preterm birth with moderate-to-severe anemia during the first trimester (more than three standard deviations [SD] below reference median hemoglobin, equivalent to less than 95 g/L at 12 weeks' gestation) was 1.68 (95% confidence interval [CI] 1.29, 2. 21). Anemia was not associated with SGA. High hemoglobin level during the first and second trimester was associated with SGA but not preterm birth. The ORs for SGA in women with very high hemoglobin level during the first and second trimester (more than three SDs above reference median hemoglobin, equivalent to greater than 149 g/L at 12 weeks' gestation and greater than 144 g/L at 18 weeks') were 1.27 (95% CI 1.02, 1.58) and 1.79 (95% CI 1.49, 2.15), respectively. CONCLUSION: These data highlight the importance of considering anemia and high hemoglobin level as indicators for adverse pregnancy outcome. An elevated hemoglobin level (greater than 144 g/L) is an indicator for possible pregnancy complications associated with poor plasma volume expansion, and should not be mistaken for good iron status.

Distribution of randomised controlled trials of drugs for post-operative nausea and vomiting.

PURPOSE: Randomised controlled trials (RCTs) guide therapeutic decisions. But which RCTs are done; which omitted; and which should be done? This study illustrates a method to explore these questions applied to drugs for post-operative nausea and vomiting (PONV). METHODS: Review articles listed 18 drugs for PONV. All RCTs of these drugs for PONV were sought. The first drug mentioned in an RCT was counted and tabulated against others in all the arms of the RCT (against itself in a dose-ranging RCT). Additional drugs mentioned in these RCTs were added to the study, for a total of 40 drugs. RESULTS: Drugs involved in the most RCTs were: ondansetron 131 RCTs; propofol 118; droperidol 74; metoclopramide 67; granisetron 52; scopolamine 22; tropisetron 16. Drugs involved in the fewest RCTs: two drugs with 2 RCTs; twelve drugs with one; three with none. Probability that this distribution occurred by chance: P < 0.00001; that the distribution of dose-ranging RCTs occurred by chance: P < 0.001. Regression of RCT numbers on cost: R = 0.86, P < 0.0001; on year of drug introduction: R = 0.14. Of 1600 possible comparisons of drugs for PONV, (including dose-ranging) 97.8% have never been published. CONCLUSION: Although some antiemetic drugs for PONV have been studied in large numbers of RCTs, many have not been adequately evaluated. Finding relevant RCTs and tabulating their comparison arms is useful for directing future research, and is applicable to any symptom or disorder.

A mutation in Rab27a causes the vesicle transport defects observed in ashen mice.

The dilute (d), leaden (ln), and ashen (ash) mutations provide a unique model system for studying vesicle transport in mammals. All three mutations produce a lightened coat color because of defects in pigment granule transport. In addition, all three mutations are suppressed by the semidominant dilute-suppressor (dsu), providing genetic evidence that these mutations function in the same or overlapping transport pathways. Previous studies showed that d encodes a major vesicle transport motor, myosin-VA, which is mutated in Griscelli syndrome patients. Here, using positional cloning and bacterial artificial chromosome rescue, we show that ash encodes Rab27a. Rab GTPases represent the largest branch of the p21 Ras superfamily and are recognized as key players in vesicular transport and organelle dynamics in eukaryotic cells. We also show that ash mice have platelet defects resulting in increased bleeding times and a reduction in the number of platelet dense granules. These defects have not been reported for d and ln mice. Collectively, our studies identify Rab27a as a critical gene for organelle-specific protein trafficking in melanocytes and platelets and suggest that Rab27a functions in both MyoVa dependent and independent pathways.

Significance of an abnormally low or high hemoglobin concentration during pregnancy: special consideration of iron nutrition.

An association between moderate anemia and poor perinatal outcomes has been found through epidemiologic studies, although available evidence cannot establish this relation as causal. Anemia may not be a direct cause of poor pregnancy outcomes, except in the case of maternal mortality resulting directly from severe anemia due to hypoxia and heart failure. Preventing or treating anemia, whether moderate or severe, is desirable. Because iron deficiency is a common cause of maternal anemia, iron supplementation is a common practice to reduce the incidence of maternal anemia. Nevertheless, the effectiveness of large-scale supplementation programs needs to be improved operationally and, where multiple micronutrient deficiencies are common, supplementation beyond iron and folate can be considered. High hemoglobin concentrations are often mistaken as adequate iron status; however, high hemoglobin is independent of iron status and is often associated with poor health outcomes. Very high hemoglobin concentrations cause high blood viscosity, which results in both compromised oxygen delivery to tissues and cerebrovascular complications. Epidemiologic studies have also found an association between high maternal hemoglobin concentrations and an increased risk of poor pregnancy outcomes. Evidence does not suggest that this association is causal; it could be better attributed to hypertensive disorders of pregnancy and to preeclampsia. The pathophysiologic mechanism of these conditions during pregnancy can produce higher hemoglobin concentrations because of reduced normal plasma expansion and cause fetal stress because of reduced placental-fetal perfusion. Accordingly, higher than normal hemoglobin concentrations should be regarded as an indicator of possible pregnancy complications, not necessarily as a sign of adequate iron nutrition, because iron supplementation does not increase hemoglobin higher than the optimal concentration needed for oxygen delivery.

Ambulatory labor epidural analgesia: bupivacaine versus ropivacaine.

UNLABELLED: Dilute concentrations of bupivacaine combined with fentanyl have recently been used to initiate labor epidural analgesia in an attempt to balance adequate analgesia and minimal maternal motor blockade. Similar concentrations of ropivacaine have not been evaluated. This prospective, randomized, double-blinded study was designed to compare the efficacy of 20 mL of either 0.08% bupivacaine plus 2 microg/mL fentanyl or 0.08% ropivacaine plus 2 microg/mL fentanyl to initiate ambulatory labor epidural analgesia. Forty nulliparous women in early ( 0 but < 20 at 20 min. The time (mean +/- SD) to visual analog scale score = 0 was BF (n = 18): 12.0 +/- 4.5 min and RF (n = 19): 12.4 +/- 4.0 min (P > 0.05). Spontaneous micturition was observed in 65% (13 of 20) BF compared with 100% (20 of 20) RF (P < 0.01), and ambulation was demonstrated in 75% (15 of 20) BF compared with 100% (20 of 20) RF (P < 0.03). The incidence of forceps delivery was 35% (7 of 20) BF compared with 10% (2 of 20) RF (P < 0.04). The results of this study indicate that dilute ropivacaine combined with fentanyl effectively initiates epidural analgesia while concurrently preserving maternal ability to void and ambulate. IMPLICATIONS: As compared with a similar dilute concentration of bupivacaine, 20 mL of dilute (0.08%) ropivacaine combined with fentanyl (2 microg/mL) effectively initiates epidural analgesia in nulliparous women in early, established labor while preserving their ability to micturate and ambulate. Of importance, it appears that a true ambulatory epidural analgesic for women in labor is now possible.

GIP biology and fat metabolism.

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), is synthesized and released from the duodenum and proximal jejunum postprandially. Its release depends upon several factors including meal content and pre-existing health status (ie. obesity, diabetes, age, etc.). It was initially discovered and named for its gastric acid inhibitory properties. However, its more physiologically relevant role appears to be as an insulinotropic agent with a stimulatory effect on insulin release and synthesis. Accordingly, it was later renamed glucose-dependent insulinotropic polypeptide because its action on insulin release depends upon an increase in circulating levels of glucose. GIP is considered to be one of the principle incretin factors of the enteroinsular axis. The GIP receptor is a G-protein-coupled receptor belonging to the family of secretin/VIP receptors. GIP receptor mRNA is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex, and brain, suggesting it may have other functions in addition to the ones mentioned above. An overactive enteroinsular axis has been suggested to play a role in the pathogenesis of diabetes and obesity. In addition to stimulating insulin release, GIP has been shown to amplify the effect of insulin on target tissues. In adipose tissue, GIP has been reported to (1) stimulate fatty acid synthesis, (2) enhance insulin-stimulated incorporation of fatty acids into triglycerides, (3) increase insulin receptor affinity, and (4) increase sensitivity of insulin-stimulated glucose transport. In addition, although controversial, lipolytic properties of GIP have been proposed. The mechanism of action of GIP-induced effects on adipocytes is unknown, and it is unclear whether these effects of GIP on adipocytes are direct or indirect. However, there is now evidence that GIP receptors are expressed on adipocytes and that these receptors respond to GIP stimulation. Given the location of its release and the timing of its release, GIP is an ideal anabolic agent and expanding our understanding of its physiology will be needed to determine its exact role in the etiology of diabetes mellitus and obesity.