Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
Does SHBG increase risk of diabetes?
Source: Ding EL, et al. N Engl J Med 2009;361:1152-1163.
Sex hormone-binding globulin (SHBG) is a protein that might seem to be most interesting to the endocrinologist, since its sole function - until very recently - has been thought to be regulation of the availability of gonadal steroids.
SHBG may have other pertinent functions. The Women's Health Study provided the data set from which the relationship between plasma SHBG and incidence of type 2 diabetes could be examined. Comparing the SHBG levels in women with newly diagnosed diabetes to controls (total n = 718), a steep inverse linear relationship between SHBG and odds ratio for developing type 2 diabetes was demonstrated. Compared to women in the lowest quartile of SHBG, those in the highest quartile were more than 10 times less likely to have incident diabetes. Corroborating results were found in men from the Physician's Health Study. The mechanism by which SHBG affects diabetes risk is speculated to be related to direct modulation of gonadal steroids on tissues, but is otherwise ill-defined.
There are identified genes associated with production of SHBG. Both SHBG levels and gene identification may become useful to predict risk of type 2 diabetes.
CRP and HTN treatment
Source: Fulop T, et al. J Am Soc Hypertens 2009;3:260-266.
C-reactive protein (CRP) is a recognized marker of inflammation, and is linearly associated with acute CV endpoints (e.g., MI, stroke). Whether this association is causal, concomitant, or consequent remains a matter of great debate. Indeed, even for advocates of the "CRP-leads-to-CVD-events" hypothesis, it remains to be determined whether interventions which specifically lower CRP reduce events, and if so, whether event reduction is secondary to CRP reduction, or another cotherapeutic effect (i.e., as in statin therapy, where CRP is reduced, but so is LDL).
Hypertension (HTN) is recognized to be the most important modifiable risk factor for CVD. Different classes of antihypertensive therapy might have different effects upon CRP. To address this, a subgroup of the Genetic Epidemiology Network of Arteriopathy study group was analyzed. In this population, 662 subjects who were on monotherapy for HTN had their CRP measured. After adjustment for a variety of other factors (e.g., age, gender, BMI, smoking, diabetes), there were distinct differences in mean CRP depending upon which class of HTN monotherapy was used. Overall, CRP levels were lowest in persons on inhibitors of the renin-angiotensin-aldosterone group (e.g., ACE inhibitor, ARB) and highest in the group on diuretics.
Current expert opinion suggests that simple blood pressure reduction is the primary effector of CV risk reduction, regardless of therapeutic class. The debate about whether therapeutic side-stream characteristics (e.g., class of agent, activity upon the renin-angiotensin-aldosterone system, metabolic effects) are important in selection of treatment will likely gain further fuel by observations that various classes of HTN treatment differ in their effect upon CRP.
Denosumab for osteoporosis
Source: Cummings SR, et al. N Engl J Med 2009;361:756-765.
It appears that osteoporosis (OSPS) is the end result of a war lost by the osteoblasts to the conquering osteoclasts, whether by frailty of the former, vociferousness of the latter, or some similar combination of factors. Indeed, our most popular tools for the prevention and treatment of OSPS - bisphosphonates - mediate improvements in bone mineral density through downregulation of osteoclasts.
Denosumab is an antibody against the activator of osteoclasts called RANKL. Once RANKL is antibody-blocked, osteoclast activity is reversibly inhibited. Denosumab is administered by subcutaneous injection every 6 months.
The study by Cummings et al enrolled almost 8000 osteoporotic women who were randomized to denosumab or placebo twice yearly for 3 years. Over that interval, a 40%-60% decrease in hip and vertebral fractures was seen (compared to placebo), with no incidence of the osteonecrosis that has been reported (albeit rarely) with bisphosphonates. The favorable tolerability of this agent (adverse effect profile similar to placebo) adds to the allure of this yet-to-be approved alternative for OSPS.
Sex hormone-binding globulin (SHBG) is a protein that might seem to be most interesting to the endocrinologist, since its sole function - until very recently - has been thought to be regulation of the availability of gonadal steroids.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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