This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

OBJECTIVE -After the demonstration that one-third of male patients with type 2 diabetes have hypogonadotrophic hypogonadism, we have shown that patients with hypogonadotrophic hypogonadism also have markedly elevated C-reactive protein (CRP) concentrations. We have now hypothesized that type 2 diabetic subjects with hypogonadotrophic hypogonadism may have a lower hematocrit because testosterone stimulates, whereas chronic inflammation suppresses, erythropoiesis.RESEARCH DESIGN AND METHODS -Seventy patients with type 2 diabetes at a tertiary referral center were included in this study.RESULTS -The mean hematocrit in patients with hypogonadotrophic hypogonadism (n ϭ 37), defined as calculated free testosterone (cFT) of Ͻ6.5 ng/dl, was 40.6 Ϯ 1.1%, whereas that in eugonadal patients (n ϭ 33) was 43.3 Ϯ 0.7% (P ϭ 0.011). The hematocrit was related to cFT concentration (r ϭ 0.46; P Ͻ 0.0001); it was inversely related to plasma CRP concentration (r ϭ 0.41; P Ͻ 0.0004). Patients with CRP Ͻ3 mg/l had a higher hematocrit (42.7 Ϯ 0.7%) than those with CRP Ͼ3 mg/l (39.9 Ϯ 1.1%; P Ͻ 0.05). The prevalence of normocytic normochromic anemia (hemoglobin Ͻ13 g/dl) was 23% in the entire group, whereas it was 37.8% in the men with hypogonadotrophic hypogonadism and 3% in the eugonadal men (P Ͻ 0.01). Erythropoietin concentration was elevated or high normal in all 11 patients with anemia in whom it was tested.CONCLUSIONS -We conclude that hypogonadotrophic hypogonadism in male type 2 diabetic subjects is associated with a lower hematocrit and a frequent occurrence of mild normocytic normochromic anemia with normal or high erythropoietin concentrations. In these patients, hematocrit is also inversely related to CRP concentration. Thus, low testosterone and chronic inflammatory mechanisms may contribute to mild anemia. Such patients may also have a high risk of atherosclerotic cardiovascular events in view of their markedly elevated CRP concentrations. Diabetes Care 29:2289 -2294, 2006A fter our previous observations that one-third of patients with type 2 diabetes have hypogonadotrophic hypogonadism (1), that type 1 diabetic subjects do not suffer from this condition (2), and that the patients with hypogonadotrophic hypogonadism have markedly elevated plasma C-reactive protein (CRP) concentrations (V.B., R.T., S.D., A. Chandel, A.C., H.G., P.D., unpublished observ a t i o n s ) , a n i n d e x o f s y s t e m i c inflammation, we have now studied whether patients with hypogonadotrophic hypogonadism have lower hemoglobin concentrations. Testosterone is known to exert a stimulatory effect on erythropoiesis in the bone marrow (3). Inflammation, on the other hand, is known to suppress erythropoiesis, partly through its direct action on erythropoiesis and partly through its suppression of erythropoietin secretion (4 -7). Thus, we hypothesized that hematocrit in patients with type 2 diabetes is lower in patients with hypogonadotrophic hypogonadism who also have an elevated CRP concentration, an index of systemic inflammation. RESEARCH DESI...

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Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and CRP concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations in type 2 diabetic men have also been related to a significantly lower hematocrit and thus to an increased frequency of mild anemia. Low testosterone concentrations are also related to an increase in total and regional adiposity, and to lower bone density. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates symptoms related to sexual dysfunction, and features of the metabolic syndrome, insulin resistance and inflammation.

PARESH DANDONA, MBBS, DPHIL 2 It is known that type 2 diabetes is frequently associated with hypogonadism in male subjects (1,2). Free testosterone concentrations are negatively related with BMI in type 2 diabetic patients (1,3). However, the relationship of free testosterone with adipose tissue mass and lean body mass in diabetic patients is not well described. Studies examining this relationship have been limited by the fact that they have not measured free testosterone by a reliable method such as equilibrium dialysis (4).Therefore, we decided to study the body composition of hypogonadal and eugonadal type 2 diabetic patients by using dual-energy X-ray absorptiometry (DEXA) to measure subcutaneous adipose tissue, lean body mass, bone mineral content (BMC), and bone mineral density (BMD). RESEARCH DESIGN AND METHODS -The study was conducted in two endocrinology practices in Midland, Texas, and Buffalo, New York. It is our practice to screen all diabetic patients for hypogonadism, due to the high prevalence of hypogonadism in diabetic patients. We also routinely evaluate body composition of our diabetic patients by DEXA (done at no cost to our patients). Therefore, informed consent was not obtained.Data from 164 consecutive male diabetic patients who presented to the endocrinology clinic were prospectively collected for the study. Patients with known history of hypogonadism; panhypopituitarism; a chronic debilitating disease such as renal failure, cirrhosis, HIV, back or hip surgery; or treatment with steroids, bisphosphonates, or recombinant parathyroid hormone were excluded. A total of 26 patients were disqualified, based on the study criteria. Therefore, data on 138 patients were included for analysis in this study. Fasting blood samples were then obtained to measure serum total testosterone, free testosterone, sex hormone-binding globulin, and A1C, using assays previously described (1). Free testosterone was measured by equilibrium dialysis (Esoterix laboratories) (normal range 0.174 -0.868 nmol/l).We measured total body mass, lean mass, subcutaneous fat mass, BMC, and BMD by DEXA (Lunar machine; General Electric Medical Systems). Measurements were made in both arms and legs and the trunk region. BMD was measured at both arms and legs, ribs, L1-L4 spine, and both hips. Hip BMD was defined as the mean BMD of both hips. Data are presented as means Ϯ SE.RESULTS -Data from 138 male type 2 diabetic subjects were analyzed. The mean age of the patients was 59.29 Ϯ 0.97 years (range 29.8 -84.3). The mean BMI was 31.83 Ϯ 0.44 kg/m 2 (18.4 -44.6). The mean total testosterone, free testosterone, and sex hormone-binding globulin concentrations were 13.29 Ϯ 0.49 nmol/l (5.17Ϫ35.97), 0.184 Ϯ 0.007 nmol/l (0.073-0.465), and 56.72 Ϯ 2.45 nmol/l (8.5-156.0), respectively. Free testosterone was inversely related to BMI (r ϭ Ϫ0.19, P ϭ 0.04) and to arm (r ϭ Ϫ0.18, P ϭ 0.05), leg (r ϭ Ϫ0.24, P ϭ 0.03), trunk (r ϭ Ϫ0.20, P ϭ 0.04), and total (r ϭ Ϫ0.23, P ϭ 0.02) subcutaneous fat mass. Total testosterone was also inversely rela...

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Atherosclerosis is currently considered to be an inflammatory and thus a systemic disease affecting multiple arterial beds. Recent advances in intravascular imaging have shown multiple sites of atherosclerotic changes in coronary arterial wall. Traditionally, angiography has been used to detect and characterize atherosclerotic plaque in coronary arteries, but recently it has been found that plaques that are not significantly stenotic on angiography cause acute myocardial infarction. As a result, newer imaging and diagnostic modalities are required to predict which of the atherosclerotic plaque are prone to rupture and hence distinguish "stable" and "vulnerable" plaques. Intravascular ultrasound can identify multiple plaques that are not seen on coronary angiography. Thermography has shown much promise and is based on the concept that the inflammatory plaques are associated with increased temperature and can also identify "vulnerable patients." Of all these newer modalities, magnetic resonance imaging has shown the most promise in identification and characterization of vulnerable plaques. In this article, we review the newer coronary artery imaging modalities and discuss the limitations of traditional coronary angiography.