July 12-15, 2017
Delano at Mandalay Bay Las Vegas,


October 11-14, 2017
Caribe Royale Orlando, Florida

MEDS eNews

Vol. 3 No. 20

Over-, under-fat terminologies
dismissed as counterproductive

KING GEORGE, VA. – Words, according to that silly-sounding line about how sticks and stones can break your bones, can’t hurt you.

There are countless issues for which that just isn’t true, weight high among them.

Take the conclusions of a study published this year in Frontiers in Public Health promoting the terms “over-fat” and “under-fat.”

The former represents excess body fat and impaired fat metabolism directly influencing health and fitness, and includes patients with excess fat in the liver, heart and muscles occurring with aging; the latter includes those with malnutrition due to starvation, with chronic illness (especially cachexia) and eating disorders.

While the study published in January recommends the use of these terms to help spur improvements in world health, nurse practitioner (NP) Christine Kessler, founder of Metabolic Medicine Associates in King George, Va., begs to differ.

Kessler, faculty co-chair of the Metabolic & Endocrine Disease Summit (MEDS), stresses that “obesity and fat are terms that come with bias,” and that “there is already too much bias within the health-care and lay communities against those with excessive weight that is keenly felt by people struggling not only with the chronic disease of obesity, but with accompanying depression. The term ‘fat,’ like obesity, is often considered pejorative.”

The NP would not like to see these terms go into use by health-care professionals, including physician assistants (PAs) and NPs, and urges that the “shame-blame” cycle in dealing with adiposity-based chronic disease (ABCD) be broken.

(ABCD is a term for obesity introduced last year by the American Association of Clinical Endocrinologists and the American College of Endocrinology.)

The study from Frontiers in Public Health notes that “over-fat” patients include those who may not be overweight or have high body mass indexes (BMIs).

The article lists a number of ways obese or unhealthy weight have been classified mostly based on metabolic health versus simply BMI. A few of these include adults who are overweight and obese with cardio-metabolic sequela; those who are metabolically obese (with metabolic syndrome) but have normal weight (MONW); those who are overweight and obese but without visceral fat and metabolic syndrome; and those with sarcopenic obesity (involving loss of skeletal-muscle mass and function, increased muscle and visceral fat accumulation that accelerates with aging).

Sarcopenic-obesity patients, Kessler says, “have been ignored, as few want to deal with the old and the fat.”  Sarcopenia is also a difficult condition to treat, and it increases the risk of falls in the elderly. “We need to better educate providers and patients,” to turn this around, she adds.

Terminology, Kessler stresses, is a “huge thing: I use adiposity, or unhealthy (or healthy) weight, not ‘obese.’ ‘Unhealthy’ is a catch-all term, and its significance is more clear.”

And while she doesn’t support the study’s conclusions on over- and under- fat terminologies, Kessler underscores its point of going beyond BMI in assessing weight challenges by recalling her experience as senior endocrinology NP at Fort Belvoir Community Hospital and Outpatient Clinics, Fort Belvoir, Va., where she treated active-and-retired military personnel “with not a lot of body fat on them.”

BMI, she says, “doesn’t give complete or accurate information,” although, she laments, insurance-reimbursement coding is BMI-based.

“That’s what we are stuck with now,” she says of this conundrum. “BMI is a risk factor, adiposity is a problem. Patients need concrete identifiers. Obesity research and management will eventually change (the BMI/coding issue). It is fine for right now.”

Definitions, she asserts, have to be followed with an open mind.

“Certain weights can be less healthy for some people than others,” she says, noting that, as a “very skinny” teen, she had to overcome weight-identity challenges.

Health-care providers, she says, “need to identify weight issues early” for patients, and, along with the general public, avoid shame-blame---which may only be reinforced through the over- and under-fat terms.

Better, she adds, to take an open approach with patients by asking, “Are you satisfied with your weight right now?”

“Losing weight,” Kessler says, “is all about unhealthy fat and reducing weight-related complications. We want patients to start thinking about the scale, and health.”

“People may shut down,” she concludes, “when they hear themselves being called ‘over-fat.’ “


CITATION: Philip B. Maffetone, Ivan Rivera-Dominguez, et. al. Overfat and Underfat: New Terms and Definitions Long Overdue. Frontiers in Public Health. 03 January 2017.


Offspring-obesity association
with GDM may differ by gender

ROCKVILLE, MD. – The association of gestational diabetes mellitus (GDM) with offspring obesity from late childhood through early adulthood may differ by sex, according to a recent study involving more than 15,000 subjects also indicating that a significant association was observed among male, but not female, offspring.

Authors of the study published in August in the International Journal of Epidemiology---including Shanshan Lee and Yeyi Zhu, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md.---noted that while data assessing animals suggests sexually-dimorphic programming of obesity in response to altered intrauterine environment, the longitudinal impact of GDM on sex-specific risk of offspring obesity in humans is unclear.

The researchers conducted a prospective analysis of 15,009 people in the United States (7,946 female, 7,063 male) from the Growing-Up Today Study (GUTS). The subjects were followed from 1996 through 2010.

Height-and-weight information obtained through validated questionnaires was used to derive body mass index (BMI) at different ages. Obesity during childhood (under age 18) and adulthood (18-and-older) was defined using the International Obesity Task Force and the World Health Organization criteria.

GDM exposure was identified through self-reported questionnaires from mothers; relative risks were estimated using multivariable log-binomial regression models with generalized-estimating equations that accounted for clustering within the same family.

Male offspring born from pregnancies complicated by GDM had higher BMI compared with non-GDM offspring and increased risk of obesity; the adjusted relative risk was 1.47 for all age groups, 1.59 for late childhood, 1.48 for adolescence and 1.39 for early adulthood.

No significant association between obesity and maternal GDM was observed among female participants.

CITATION: Shanshan Li, Yeyi Zhu, et. al. Offspring risk of obesity in childhood, adolescence and adulthood in relation to gestational diabetes mellitus: a sex-specific association. International Journal of Epidemiology. 09 August 2017.


Study: Furosemide does not reduce
worsening AKI rate, or aid recovery

EDMONTON, ALBERTA – Recently-published research indicates that furosemide does not reduce the rate of worsening acute kidney injury (AKI), improve recovery, or reduce renal replacement therapy (RRT).

The study published in July in the Journal of Critical Care did, however, indicate that furosemide is associated with greater electrolyte abnormalities.

Its authors---including Sean M. Bagshaw and R.T. Noel Gibney, who are affiliated with the University of Alberta, Edmonton, Alberta---noted that furosemide is commonly prescribed to patients with AKI in intensive-care unit (ICU) settings.

The pilot randomized controlled trial (RCT) was designed to evaluate the impact of furosemide in early AKI on worsening AKI, kidney recovery, and RRT use.

No differences were found in the proportion with worsening AKI, kidney recovery, or RRT use.

Adverse events, driven largely by electrolyte abnormalities, more commonly occurred in furosemide-treated patients.

The researchers utilized a multi-center randomized blinded placebo-controlled trial in adult patients with AKI admitted to three ICUs.

Participants were randomly allocated to furosemide bolus and infusion or 0.9% saline placebo. Primary endpoint was worsening AKI, defined by RIFLE criteria.

Secondary endpoints were kidney recovery, RRT, and adverse events.

The trial was terminated after enrollment of 73 participants (37 to furosemide and 36 to placebo).

Mean standard deviation (SD) age was 61.7; 79.5% were medical admissions; mean (SD) APACHE II score was 26.6 (7.8), 90.4% received mechanical ventilation, and 61.6% received vasoactives.

Groups were similar at baseline.

Protocol deviations were common, due often to supplementary furosemide.


CITATION: Sean M. Bagshaw, MD, MSc, R.T. Noel Gibney, MD, et. al. The effect of low-dose furosemide in critically ill patients with early acute kidney injury: A pilot randomized blinded controlled trial (the SPARK study). Journal of Critical Care. Published online: July 12, 2017.


Lower QOL for osteoporosis patients
could be linked to thoracic kyphosis

AKITA, JAPAN – Lower quality of life (QOL) in osteoporosis patients may be associated with increased thoracic kyphosis, reduced lean-muscle mass, and generalized muscle weakness, according to a study published in August in Osteoporosis International.

Its authors---including Naohisa Miyakoshi and Daisuke Kudo, Akita University Graduate School of Medicine, Akita, Japan---compared spinal alignment, muscular strength, and QOL between women with post-menopausal osteoporosis and healthy volunteers.

Participants comprised 236 female patients with post-menopausal osteoporosis (mean age, 68.7 years) and 93 healthy volunteer women (mean age, 71.0 years).

Body mass index (BMI), angles of spinal kyphosis, back-extensor strength, grip strength, and QOL were compared between groups.

BMI, back-extensor strength, and grip strength were significantly higher in the volunteer group than in the osteoporosis group, while thoracic kyphosis and lumbar lordosis were significantly greater in the osteoporosis group than in the volunteer group.

Regarding QOL, the 36-Item Short-Form Health Survey (SF-36) sub-scale scores of role physical, bodily pain, general health, and role emotional were all significantly lower in the osteoporosis group than in the volunteer group.

SF-36 physical component summary (PCS) score was significantly lower in the osteoporosis group than in the volunteer group.

SF-36 PCS score correlated positively with thoracic kyphosis and negatively with BMI only in the osteoporosis group.


CITATION: N. Miyakoshi, D. Kudo, et. al. Comparison of spinal alignment, muscular strength, and quality of life between women with postmenopausal osteoporosis and healthy volunteers. Osteoporosis International. First online: 07 August 2017.


Significant proportion of hospitalizations
associated with non-diabetic hypoglycemia

TOKYO – A study involving more than 8,600 subjects indicates that non-diabetic hypoglycemia accounts for a significant proportion of hospitalizations with hypoglycemia.

The research published in June in Medicine showed an in-hospital mortality rate as high as 14.9% and higher than that of diabetic hypoglycemia.

Its authors---including Hideo Yasunaga, who is affiliated with The University of Tokyo---report that disease burden and clinical importance are not ignorable, and suggest that clinicians carefully examine the etiology of hypoglycemia in patients without diabetes mellitus, and treat the underlying causes.

Using the Diagnosis Procedure Combination (DPC) data-base, the researchers set out to examine prevalence, patient characteristics, etiology, and clinical outcomes of hospitalized patients who had hypoglycemia without a diagnosis of diabetes mellitus.

The retrospective observational study of acute-care inpatients in Japan assessed non-diabetic patients aged 15-years-and older who were hospitalized for hypoglycemia.

The authors estimated the annual numbers of hospitalized cases in Japan and investigated patient characteristics and risk factors of in-hospital mortality.

They identified 8,684 eligible patients out of 22.7 million discharge records between July, 2008, and March, 2013; average age was 70.0 years and the average body mass index (BMI) was 19.9 kg/m2.

Most frequently-recorded underlying diseases were:

  • malignancies

  • cerebrovascular diseases

  • pneumonia

  • renal failure

  • heart failure

The estimated annual numbers of hospitalizations due to hypoglycemia in non-diabetic patients were 5000 to 7000.

In-hospital mortality was 14.9%.

Predictive factors for poor survival included:

  • older age

  • community hospital

  • low BMI

  • coma at admission

  • urgent admission

  • renal failure

  • heart failure

  • pneumonia

  • sepsis

  • chronic liver diseases

  • malignancies

Patients without diabetes mellitus but with hypoglycemia had multiple comorbidities and high in-hospital mortality.

CITATION: Sako, Akahito MD, MPH; Yasunaga, Hideo MD, Ph.D., et. al. Hospitalization with hypoglycemia in patients without diabetes mellitus: A retrospective study using a national inpatient database in Japan, 2008–2012. Medicine. June 2017-Volume 96-Issue 25—p e 7271.


Possible hip-CT scan benefits
discussed in Clinician Reviews

Computed tomography (CT) scans taken for unrelated reasons might potentially be used for osteoporosis screenings, according to a study discussed recently at the annual American Society for Bone and Mineral Research (ASBMR) in Denver. As reported in September in Clinician Reviews, researchers conducting a case-control cohort analysis of patients 65-and-older who were seen at 11 Kaiser Permanente Southern California (KPSC) hospitals analyzed CT-scan data producing estimates of bone mineral density (BMD) and femoral strength. These performed similarly to dual-energy X-ray absorptiometry (DXA) in predicting fracture risk; 1,340 women and 619 men had their first hip fractures during the study period. The article can be accessed at



Vol. 3 No. 19

‘We need to get the word out’
on the challenges of ADPKD

OCEANSIDE, CALIF. – Autosomal dominant polycystic kidney disease (ADPKD), one of the most common genetic diseases, presents a special challenge---the difficulty in convincing non-nephrology health professionals that there is such a thing as an ADPKD diagnosis.

ADPKD occurs in about one in every 400-to-1,000 live births, and is relatively unknown outside of the kidney community. Timely diagnosis can slow cyst growth and decrease end-stage organ damage, extending patients’ lifespans and delaying the necessity for transplantation or dialysis. The disease is often clinically silent, and less than half of patients who have it are diagnosed during their lifetimes.

Ultrasonography is most commonly used for imaging, though genetic testing can be used for definitive diagnosis in some settings.
ADPKD is suspected when patients present with symptoms related to the large kidneys associated with hypertension (HTN), flank pain of hematuria, palpable kidneys or liver, or subarachnoid hemorrhage; it is sometimes diagnosed incidentally when an ultrasound is performed for unrelated reasons, such as pregnancy.

And, notes, Kim Zuber, PA-C, a retired physician assistant (PA) and past chair of the National Kidney Foundation/Council of Advanced Practitioners, “there are more people with ADPKD than Tay-Sachs, Down Syndrome, Duchenne muscular dystrophy, and sickle-cell disease added together.”

Zuber, of Oceanside, Calif., a faculty member of the Metabolic & Endocrine Disease Summit (MEDS), notes that when her daughter was in the sixth grade, her class did a science project on genetic diseases, and “ADPKD wasn’t listed as a genetic disease.”

Zuber’s take on the difficulty in convincing health practitioners to acknowledge ADPKD is echoed in a recent study published in BMC Nephrology noting the difference between patients’ understanding of the disease and what they believe their doctors tell them.

The classic patient presenting with ADPKD has high blood pressure, and urinates blood; it is diagnosed more often in males, who are more likely to report this to physicians than females, who may mistake this symptom for menstruation.

About 78% of families with ADPKD have an abnormality on chromosome 16.

Nephology professionals, Zuber says, “have also found that at the beginning of the HTN-only phase (at early age when just HTN is diagnosed), these patients often have a glomerular filtration rate (GFR) of more than 120ml/min, and thus the idea of kidney disease never enters the practitioners’ minds.”

Practitioners, Zuber says, don’t generally look for secondary causes when treating patients for HTN.

The kidney expert recalls treating a family with six children in which the mother wasn’t diagnosed with ADPKD until age 68; four of her six children had the gene, including one who received a kidney from his father when he was 13.

Zuber also treated a policeman with the disease whose kidneys had become so large he couldn’t buckle his safety vest.

Furthering patient understanding of ADPKD as well as increasing health-care professionals’ awareness, she says, can be achieved by:

  • patient outreach, including efforts on the part of PAs and nurse practitioners (NPs)
  • articles in print and online
  • public presentations; Zuber raises the issue when she gives talks
  • efforts by patients diagnosed with the disease to push for ultrasounds for other family members

On the latter matter, though, Zuber notes that while ultrasound testing may be pushed for those 30 or older, there exists the danger that, with testing for younger patients, a patient may subsequently run into insurance problems tied to pre-existing conditions.

Zuber also points to two major studies published in 2014 in the New England Journal of Medicine by the HALT-PKD trial investigators. These multi-year, multi-center National Institutes of Health (NIH)-sponsored studies of patients with early-to-late kidney disease show that early and aggressive treatment of hypertension will slow progression of the cysts in ADPKD, thus saving patients years of dialysis treatment. In late kidney disease, aggressive hypertension treatment is not as effective, although statin treatment was found to save lives by decreasing cardiac endpoints.  

Thus, the importance of getting the non-kidney medical community to become more aware and aggressively treat early ADPKD is highlighted by Zuber.
“We need to get the word out,” she says.

CITATION: Wen-Ching Tran, David Huynh, et. al. Understanding barriers to medication, dietary, and lifestyle treatments prescribed in polycystic kidney disease. BMC Nephrology 201718:214. Published online 2017 July 5. PMCID: PMC5498983 Robert W. Schrier, M.D., Kaleab Z. Abebe, Ph.D., et. al. Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease. New England Journal of Medicine. December 11, 2014. Vincente E. Torres, M.D., Ph.D., Kaleab Z. Abebe, Ph.D., et. al. Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease. New England Journal of Medicine. December 11, 2014. Jacob A Akoh. Current management of autosomal dominant polycystic kidney disease. World Journal of Nephrology. September 6, 2015. Davies D, Coles GA, et. al. Polycystic kidney disease re-evaluated: a population-based study. Q J Med. 1991 Jun;79(290):477-85. PMID: 19462928. Diagnosis of and screening for autosomal dominant polycystic kidney disease.


Abdominal-obesity indicators
could predict hip-fracture risk

QINGDAO, CHINA – A recently-published meta-analysis suggests that abdominal obesity as measured by waist circumference and waist-hip ratio might be associated with increased hip-fracture risk.

The study published in July in Osteoporosis International indicates that, from a public-health perspective, indicators of abdominal obesity may be usable predictors of hip-fracture risk.

Its authors---including Wenjie Jiang, who is affiliated with Qingdao University, Qingdao, China---set out to qualitatively summarize the evidence of the association between abdominal obesity and hip-fracture risk.

They searched PubMed, Embase, and Web of Science for relevant articles published up to March, 2017; pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model.

Dose-response relationship was assessed by restricted cubic spline.

Included for meta-analysis:

  • seven studies involving 180,600 participants for hip circumference
  • six involving 199,828 participants for waist-hip ratio
  • five involving 170,796 participants for waist circumference

The combined RRs with 95% CIs of hip fracture for the highest-versus-lowest category of waist circumference, waist-hip ratio, and hip circumference were 1.58 (95% CI 1.20–2.08), 1.32 (95% CI 1.15–1.52), and 0.87 (95% CI 0.74–1.02), respectively.

For dose-response analysis, a non-linear relationship was found between waist circumference and hip-fracture risk.

A linear relationship suggested that this risk increased about 3.0% (1.03 [1.01–1.04]) for each 0.1 unit increment of waist-hip ratio.

CITATION: X. Li, X. Gong, et. al. Abdominal obesity and risk of hip fracture: a meta-analysis of prospective studies. Osteoporosis International. pp 1-11. First Online: 12 July 2017.



Clinical investigation connects
low vitamin D, poorer cognition

MELBOURNE, AUSTRALIA – Observational evidence from a recently-published clinical investigation demonstrates that low vitamin D is related to poorer cognition---while also indicating that interventional studies have yet to show a clear benefit from vitamin D supplementation.

The research published in July in the Journal of the American Geriatrics Society also notes that, from the evidence to date, there is likely a therapeutic age window relevant to the development of disease, and therefore, vitamin D therapy.

Its authors---including Alicia M. Goodwill and Cassandra Szoeke, Australian Catholic University, Melbourne, Australia---note that longitudinal lifespan studies are necessary to depict the optimal timing and duration in which repletion of vitamin D may protect against cognitive decline and dementia in aging.
Their systematic review and random-effect meta-analysis examined the effect of low vitamin D status or vitamin D supplementation on cognition in midlife-and-older adults without a diagnosis of dementia.

They utilized observational (cross-sectional and longitudinal cohort) studies comparing low-and-high vitamin D status, and interventions comparing vitamin D supplementation with a control group; studies including adults and older adults without a dementia diagnosis were included.

Medline (PubMed), AMED, PsycINFO, and Cochrane Central data-bases were searched for articles until August, 2016.

The Newcastle-Ottawa Scale and Physiotherapy Evidence Database assessed methodological quality of all studies.

Twenty-six observational and three intervention studies were included in the meta-analysis.

Low vitamin D was associated with worse cognitive performance and cognitive decline, with cross-sectional yielding a stronger effect compared to longitudinal studies.

Vitamin D supplementation showed no significant benefit on cognition compared with control.

CITATION: Alicia M. Goodwill, Ph.D., Cassandra Szoeke, Ph.D. A Systematic Review and Meta-Analysis of The Effect of Low Vitamin D on Cognition. Journal of the American Geriatrics Society. First published: 31 July 2017.;jsessionid=726E87B51289821A6DF029104462821B.f02t02


Parathyroid-tumor behavior may
help foretell severity of disease

DURHAM, N.C. – Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density (BMD) deficit, according to a recent study indicating that assessment of parathyroid-tumor biochemical behavior may be a useful predictor of disease severity as measured by BMD in patients with primary hyperparathyroidism (PHPT).

The study published in June in Metabolism Clinical and Experimental was designed to identify new mechanistic indices that could inform more personalized PHPT management.

Its authors---including Thomas J. Weber and James Koh, Duke University Medical Center, Durham, N.C.---collected pre-, peri-, and post-operative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT; univariate and partial Spearman correlation was used to estimate the association of parathyroid-tumor calcium-sensing capacity with select variables.

Their research involved an un-selected series of 237 patients over the age of 18 undergoing parathyroidectomies for PHPT.

Calcium-sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an un-selected series of 74 patients and assessed for association with clinical parameters.

The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically-autonomous parathyroid-tumor behavior.

The authors found parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50 less than 3.0, and at least 3.0 mM).

The low EC50 group (27 patients) demonstrated a mean calcium EC50 value of 2.49 mM (95% confidence interval [CI]: 2.43–2.54 mM), consistent with reference normal activity.

The high EC50 group (47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48 mM (95% CI: 3.41–3.55 mM).

Retrospective analysis of clinical-registry data suggested that high-calcium EC50 patients presented with a more significant pre-operative BMD deficit with a t-score of −2.7, (95% CI: −3.4 to −1.9) versus 0.9, (95% CI: −2.1 to −0.4) in low EC50 patients.

After adjusting for gender, age, body mass index (BMI), 25 OH vitamin D level and pre-operative intact PTH (iPTH), lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of −0.35.

CITATION: Thomas J. Weber, James Koh, et. al. Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density. Metabolism Clinical and Experimental. Published online: June 18, 2017. Accepted: June 14, 2017. Received: March 22, 2017.


With reservations, researchers link
alcohol consumption, diabetes risk

COPENHAGEN, DENMARK – The findings of a recent study suggest that alcohol-drinking frequency is associated with diabetes risk, and that alcohol consumption over three-or-four-days per week is associated with the lowest diabetes risk---even after accounting for weekly-alcohol consumption.

The study published in July in Diabetologia assessed the association between alcohol-drinking patterns and diabetes risk in men and women from survey data from 70,551 men and women from the general Danish population.

Its authors, including Charlotte Holst and Ulrik Becker, University of Southern Denmark, Copenhagen, Denmark, based their cohort study on data from the Danish Health Examination Survey 2007-to-2008.

However, the study’s senior author, Janne S. Tolstrup, in comments made to Reuters Health News, cautions that these results don’t imply that non-drinkers should start drinking “for their health.”

Of the 76,484 survey participants, 28,704 men and 41,847 women were eligible for this study. Participants were followed for a median of 4.9 years.

Self-reported questionnaires were used to obtain information on such alcohol-drinking patterns as frequency of alcohol drinking, frequency of binge drinking, and consumption of wine, beer and spirits, from which the authors calculated beverage-specific and overall average weekly-alcohol intake.

Information on incident cases of diabetes was obtained from the Danish National Diabetes Register.

During follow-up, 859 men and 887 women developed diabetes.

The lowest risk of diabetes was observed at 14 drinks per week for men and nine per week for women, relative to no alcohol intake.

Compared with current alcohol consumers consuming less than one-day-per-week, alcohol consumption three-or-four days a week was associated with significantly lower risk for diabetes in men and women, after adjusting for confounders and average weekly alcohol amount.

But while the study suggests that those who spread out their drinking are less likely to develop diabetes than those who do all their drinking on one night, senior study author Tolstrup, University of Southern Denmark, cautions that non-drinkers shouldn’t start drinking “for their health.”

A similar message comes from Tim Stockwell, director of the Center for Addictions Research of BC, Victoria, British Columbia, Canada, who cites health risks associated with even moderate alcohol use and urges, in remarks made to Reuters Health News, skepticism about drinking as a means to protect against diabetes.

CITATION: Charlotte Holst, Ulrik Becker, et. al. Alcohol drinking patterns and risk of diabetes: a cohort study of 70,551 men and women from the general Danish population. Diabetologia. pp 1-10. First online: 27 July 2017. Can a drink a day keep diabetes away? Reuters Health News.

Thyroid storm is addressed
in Clinician Reviews article

An article published in August in Clinician Reviews addresses thyroid storm, a serious medical condition with a high mortality rate. Written by Ji Hyun Chun (CJ), PA-C, BC-ADM, Optum Medical Group, Laguna Niguel, Calif., the piece recounts the case of a 73-year-old man taken to an emergency department (ED) for nausea, vomiting, diarrhea, and weakness of three days’ duration. Chun concludes that prompt recognition and an aggressive multi-modal treatment approach, ideally in the intensive care unit (ICU), are keys to stabilize patients and seek definitive treatment for this extreme form of thyrotoxicosis. The article can be accessed at


Vol. 3 No. 18

Boost in public awareness urged
by expert in skeletal-health issues

SOUTHBURY, CONN. – Public awareness of skeletal health’s urgency needs an upgrade.

That’s the assertion of an osteoporosis expert who says health-care professionals---notably physician assistants (PAs) and nurse practitioners (NPs)---and, hopefully, a celebrity or two, can help open a larger window into the importance of bone issues.

Rick Pope, (PA)-C, Department of Rheumatology, Western Connecticut Medical Group, Danbury, Conn., says NPs and PAs “can reach out to patients” to battle “under-recognition and under-treatment.”

Pope, a Southbury, Conn., resident, founder and past three-time president of the Society of Physician Assistants in Rheumatology (SPAR), and faculty member of the Metabolic & Endocrine Disease Summit (MEDS) says skeletal health is among “the last things primary-care providers discuss with patients. Weight, exercise, the need for older patients to stop smoking, not to drink excessively, come up instead. Practitioners don’t put osteoporosis high up on their list, even though it is now easier to manage with bone density and meds.”

He sees the need for “a pre-eminent leader in some area” to increase awareness, noting, for instance, actress Sally Field, who publicized her battle with osteoporosis.

“We need money to be made available to promote awareness, via Facebook, PBS, social media. We need more awareness that poor skeletal health can kill you. It leads to a downward spiral. It’s an older person’s nightmare.”

One such nightmare, the most common fracture among osteoporosis patients, is that of vertebral compression fractures (VCFs). Pope says systematic VCF management lends itself to “four tenants”:

  • provide bed rest for most severe pain for a short period of time
  • pharmacological solutions such as acetaminophen and opioids. Regarding the latter, Pope notes that medical practitioners are “more cautious” with these because of side effects and increased fall risk. He suggests milder ones, and, for those with codeine, such precautions as using them at certain times of day
  • posture support (such as braces)
  • physical therapy

Regarding VCFs, Pope agrees with an International Osteoporosis Foundation (IOF) review of balloon kyphoplasty and vertebroplasty (both involving placement of cement into a fractured vertebra) in managing VCFs.

The IOF noted that the “long-term risks of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting.” Pope sees a need for more randomized studies about both cementing procedures and says he has seen “the pendulum swing for these procedures, first a downward spiral then an upward swing. We need more studies to show what they mean for patients.”

The cases of two of Pope’s patients bear this out:

  • A 62-year-old retired nurse with aggressive rheumatoid arthritis who became heavy and less mobile from prednisone. She experienced bladder dysfunction and eventually underwent vertebroplasty, after which she voided 800-to-1,000 ccs. “She needed this procedure,” Pope concludes.
  • An 85-year-old woman with post-menopausal osteoporosis as well as scoliosis, who then developed severe acute back pain. She has co-morbidities of diabetes, hypertension and heart disease. Surgery was ruled out; however, there was another treatment possibility, an injection of salmon calcitonin, which was rejected due to its cost. Instead, she received physical therapy at home, plus acetaminophen. (Pope adds in hindsight that he should have considered calcitonin nasal spray, which would have likely been less expensive and approved by insurance)

Pope concurs with a conclusion of a study published this year in the Global Spine Journal that there is a lack of standard of care for osteoporotic VCF patients along with treatment recommendations, including a comment that most American Academy of Orthopedic Surgeons (AAOS) clinical-practice guidelines on the issue are weak or inconclusive.

“Further studies,” he says, “are needed to clarify when surgery is needed: 12-and-24-month-and-longer, high-level studies.”

Also needed is medical help like that offered in two drugs he mentions.

One, involving sclerostin-antibody treatment for osteoporosis and developed by Amgen, is not yet on the market, while another, from Radius Health Inc., is Tymlos, an injection for the treatment of post-menopausal women with osteoporosis who are at high-fracture risk, which received Food and Drug Administration (FDA) approval this year.

“There is a great variety of approaches to medical management, and now these two surgical procedures for VCFs are making a comeback,” Pope concludes. “It depends largely on the situation with the orthopedic surgeon or interventionalist in the local community.”

CITATION: Ivo K. Genev, Matthew K. Tobin, et. al. Spinal Compression Fracture Management. A Review of Current Treatment Strategies and Possible Future Avenues. Global Spine Journal. 2017 Feb; 7(1): 71–82. Published online 2017 Feb. 1. PMCID: PMC5400164. PMCID: PMC5400164. Borgström F1, Olafsson G, et. al. The impact of different health dimensions on overall quality of life related to kyphoplasty and non-surgical management. Osteoporosis International. 2013 Jul;24(7):1991-9. Epub 2013 Apr 27.  Boonen, S., Wahl, D.A., et. al. Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures. Osteoporosis International. 2011. 22:2915.

Research on lesions indicates
the possibility of misdiagnosis

NEW YORK – Lesions with follicular lesion of undetermined significance-like or oncocytic features are prone to misdiagnosis, according to a study published in June in Cancer Cytopathology.

The study---whose authors include Margaret Cho and Thaira Oweity, New York University Langone Medical Center, New York---identified distinct cytologic patterns in parathyroid lesions suggestive of parathyroid origin, which, together with parathyroid hormone (PTH) immunostains or assay, molecular studies, or sestamibi scans, aid in distinguishing parathyroid from thyroid lesions. 

The researchers noted that differentiating parathyroid and thyroid lesions can be challenging because of considerable morphologic overlap and anatomic proximity, and set out to identify characteristic morphologic patterns and useful adjunct tests to distinguish these two entities.

A data-base search was conducted for clinically-indeterminate thyroid nodules from 2000 through 2016, with an emphasis on confirmed parathyroid nodules.

Pathology reports, slides, ancillary studies, molecular analysis, and clinical-and-radiologic data were retrieved.

A total of 143 cases of clinically-indeterminate thyroid nodules were identified; 34 were confirmed parathyroid nodules.

Three cytologic patterns were identified:

  • oncocytic cell pattern (nine cases, 26%)
  • follicular lesion of undetermined significance-like/papillary-like pattern (14 cases, 41%)
  • non-specific endocrine cell clusters (11 cases, 32%)

Bare oval nuclei (100%), nuclear overlap (88%), crowded sheets (88%), and intracytoplasmic vacuoles (62%) were observed.

Ten cases (29%) demonstrated positive immunostaining for PTH; seven (21%) demonstrated a positive PTH assay; and nine (26%) had PTH detected by ThyroSeq v.2.

The remaining eight cases were morphologically either indeterminate or suggestive of parathyroid origin.

The cytologic diagnosis was confirmed clinically (20 cases) or surgically (14 cases). Based on cytology alone, eight cases were initially diagnosed as thyroid tissue and amended to parathyroid lesion after ancillary studies were performed, including five cases based on ThyroSeq v.2 results alone.


CITATION: Margaret Cho MD, Thaira Oweity MD, et. al. Distinguishing parathyroid and thyroid lesions on ultrasound-guided fine-needle aspiration: A correlation of clinical data, ancillary studies, and molecular analysis. Cancer Cytopathology. First published: 16 June 2017. Version of record online: 16 June 2017. Manuscript Accepted: 16 May 2017. Manuscript Revised: 12 May 2017. Manuscript Received: 28 April 2017.



Study shows increased CVD risk
is associated with hypoglycemia

WORCESTER, MASS. – A recent study provides evidence of increased cardiovascular-disease (CVD) risk associated with hypoglycemia---especially serious hypoglycemia events.

The study published in May in Diabetes, Obesity and Metabolism indicates that while associations were attenuated with non-serious hypoglycemia, the results suggested a potential increased risk.

Its authors, including Kristy Iglay, University of Massachusetts Medical School, Worcester, Mass., noted that certain treatments for type 2 diabetes mellitus cause hypoglycemia and weight gain, and thus might counteract the benefits of intensive glucose control.

The researchers quantified the association of CVD outcomes with hypoglycemia and weight gain among type 2 diabetes patients treated with sulfonylureas.

The cohort study included patients from January, 2009, through December, 2014, identified within a de-identified nationwide electronic-health records repository, including multiple-provider networks and electronic-medical records systems.

Hypoglycemia measures from structured data fields and free-text clinical notes were categorized as serious or non-serious.

Covariate adjusted Poisson regression analysis was used to assess the association between the frequency of hypoglycemia (by severity), or magnitude of weight change, and incidence of acute myocardial infarction (AMI), congestive heart failure (CHF), and stroke.

Among 143,635 eligible patients, the researchers observed:

  • 5,669 cases of AMI
  • 14,109 incident cases of CHF
  • 7,017 strokes

Overall incidence rates were 1.53, 4.26, and 1.92 per 100 person-years for AMI, CHF, and stroke, respectively.

The associations between overall hypoglycemia and each of the CVD outcomes were positive, with stronger associations observed for serious hypoglycemia and attenuated or null associations observed for non-serious hypoglycemia.

Weight change exhibited a U-shaped association with increased risks associated with both weight loss and weight gain relative to stable weight.

CITATION: Anthony P. Nunes Ph.D., Kristy Iglay Ph.D., et. al. Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users. Diabetes, Obesity and Metabolism. Accepted manuscript online: 12 May 2017. Manuscript accepted: 30 April 2017. Manuscript revised: 28 April 2017. Manuscript received 9 January 2017.

Lower danger of mortality seen
for overweight diabetes patients

BEIJING – A meta-analysis of 20 studies involving more than 250,000 patients showed a significantly lower risk of all-cause mortality in overweight patients with diabetes compared to normal-weight patients.

The study published in June in the Journal of Diabetes Investigation also indicates that the survival benefits of obesity were only observed among elderly patients.

Its authors---including Fei Gao and Zhi Jian Wang, who are affiliated with An Zhen Hospital, Capital Medical University, Beijing---report that the more-pronounced beneficial prognostic impact of obesity was attenuated with longer follow-up durations.

The researchers also note that caution should be taken in interpreting the results, as the study’s design didn’t permit verification of the causal relationship between body weight and prognosis in patients with diabetes, and urged further studies.

Their assessment included searches of the OVID/MEDLINE, EMBASE and Cochrane data-bases for all reported studies investigating the relationship between body mass index (BMI) and mortality in diabetes patients.
Summary estimates of hazard ratios (HRs) were obtained with a random-effects model; univariate meta-regressions were carried out.

A total of 20 studies including 250,016 patients with diabetes were identified. The results of the present study showed a significantly reduced risk of all-cause mortality as compared to normal-weight patients.

The survival benefits of obesity were only observed in the elderly patients.

The beneficial prognostic impacts on overweight and obesity were attenuated with clinical follow-up duration.

Also: A study published in March in Drugs & Aging involving more than 8,000 subjects indicates that the dose-response for statins on new-onset of diabetes suggests that elderly women should not be exposed to higher doses of statins. The study can be accessed at

CITATION: Fei Gao, Zhi Jian Wang, et. al. Impact of obesity on mortality in patients with diabetes: Meta-analysis of 20 studies including 250,016 patients. Journal of Diabetes Investigation. Version of record online: 8 June 2017. Manuscript Accepted: 4 April 2017. Manuscript Revised: 28 March 2017. Manuscript Received: 3 February 2017.

Gluten avoidance may spur decrease
in beneficial whole-grain consumption

NEW YORK – Long-term dietary gluten intake was not associated with coronary heart-disease risk in a prospective-cohort study that also indicated that gluten avoidance may cause reduced beneficial-whole grain consumption.

The study published in May in BMJ also indicates that while people with-and-without celiac disease may avoid gluten because of a symptomatic response to this dietary protein, its findings don’t promote a gluten-restricted diet with a goal of reducing coronary-heart disease risk.

Its authors, including Benjamin Lebwohl, Columbia University College of Physicians and Surgeons, New York, and Yin Cao, Harvard Medical School, Boston, report that dietary- gluten avoidance may result in a low intake of whole grains, which are associated with cardiovascular benefits.

The researchers also state that the promotion of gluten-free diets for the purpose of coronary heart-disease prevention among asymptomatic people without celiac disease should not be recommended.

Their study involved 64,714 women in the Nurses’ Health Study and 45,303 men in the Health Professionals Follow-up Study without a history of coronary heart disease.

Among those 110,017 subjects eligible for analysis, the mean daily-estimated intake of gluten at baseline was 7.5 (standard deviation [SD] 1.4) g among women and 10.0 (2.0) g among men in the highest fifth, and 2.6 (0.6) g among women and 3.3 (0.8) g among men in the lowest fifth.

In 2010, the mean daily-estimated gluten intake was 7.9 (2.4) g among women and 9.2 (2.8) g among men in the highest fifth, and 3.1 (1.2) g among women and 3.7 (1.3) g among men in the lowest fifth.

Gluten intake correlated inversely with alcohol intake, smoking, total-fat intake, and unprocessed red-meat intake.

Gluten intake correlated positively with whole-grain intake and refined-grain intake; gluten did not correlate strongly with sodium intake.


CITATION: Benjamin Lebwohl, Yin Cao, et. al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ. 2017;357: j1892. Published 02 May 2017.

Sweetened beverage-diabetes risk
assessed in Clinician Reviews article

An article published in July in the Clinical Edge section of Clinician Reviews takes on the topic of sweetened-beverage consumption and diabetes risk. Quoting a study published online in June in The American Journal of Clinical Nutrition, the article notes that artificially-sweetened beverages (ASBs) are associated with a 21% increased risk of developing diabetes mellitus (DM), about half the magnitude of sugar-sweetened beverages (SSBs, a 43% increased risk). The prospective Women’s Health Initiative observational study also indicates that replacing either ASBs or SSBs with water can potentially reduce this risk. The article can be accessed at


Vol. 3 No. 17

In testosterone-osteoporosis link,
a cautious approach is suggested

LAGUNA NIGUEL, CALIF. – A recent study on male hypogonadism and osteoporosis focuses on clinical consequences, effects, and treatment of testosterone deficiency in bone health…and, says one expert medical professional, raises issues that should be cautiously addressed.

Ji Hyun Chun (CJ), PA-C, BC-ADM, OptumCare Medical Group, Laguna Niguel, Calif., has his own take on a statement in the study published in March in the International Journal of Endocrinology that hypogonadal males should be aware of the fact that those treated with testosterone have significant bone-density gains in short time periods.

Chun, president-elect of the American Society of Endocrine Physician Assistants (ASEPA) and a faculty member of Metabolic & Disease Summit (MEDS), says clinicians “often focus on patients’ sexual symptoms, overall well-being, and testosterone levels, and impact on bone mass density (BMD) is not often considered.”

Chun adds that “it is crucial for clinicians to recognize low testosterone as a possible secondary etiology of male osteoporosis if the patient presents with fracture and/or low BMD.”

The physician assistant (PA) says BMD tests “should be considered for patients with profound hypogonadism, especially if you suspect hypogonadism might have been going on for a while: You should also ask about fracture history, height loss, and back pain.”

The study’s mention that the risk of falls and fracture risk among elderly men is associated with lower testosterone levels also spurs circumspection on Chun’s part.

“Testosterone levels,” he asserts, “can drop or fluctuate for various reasons, and often are suppressed when the body is stressed for some reason.”

Chun says that while those causes may relate to the frail elderly (seniors with other comorbidities), there may be a “chicken-or-the-egg” relationship: Are they frail because of low testosterone, or do they have low testosterone because they are elderly and frail?

“Frail elderly,” he says, “are at higher risk for falls due to lack of balance and strength; again, is this due to low testosterone or just their overall frail status? Hard to distinguish.”

Chun points to two research efforts on the subject: a clinical trial of testosterone treatment in older men (its treatment phase was dropped in 2010 because of a higher rate of adverse cardiovascular events among older men receiving testosterone gel compared to those getting placebo), and another, reported this year, on testosterone treatment and coronary artery plaque volume among older men with low testosterone.

The latter study, Chun points out, indicates that neither physical function nor vitality improved significantly on testosterone as compared with placebo among 170 men aged 65-and-older (88 received testosterone).

While acknowledging that men with profoundly-low testosterone levels may experience bone loss, Chun says that age-related hypogonadism-testosterone levels rarely fall to that range. Yet, it may be helpful for health-care providers to make patients aware of hypogonadism-BMD considerations.

The BMD tie-in, he says, “might be something that is not thought of as often as that of sexual function.”

As to treatment, Chun says, “those with pathologic hypogonadism (pituitary or testicular surgery or radiation, or genetic disorders), with profound hypogonadism, patients who have low BMD, I think it is very reasonable to put them on testosterone replacement therapy (TRT) and monitor their BMD. Hopefully, we can catch it early enough, before they develop osteoporosis. And for those with high risk of fracture, or who already have fractures, I would definitely consider adding osteoporosis medications as well.

Finally, Chun says “there are cases where we intentionally lower testosterone levels (such as in prostate-cancer management) to almost zero. It is suggested that we use bisphosphonates to prevent bone loss while they are on that therapy. Obviously, TRT can’t be used during that time.”

CITATION: Gary Golds, Devon Houdek, et. al. Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health. International Journal of Endocrinology. March 2017. Volume 2017 (2017), Article ID 4602129, 15 pages. Review article. Adverse Cardiovascular Events Reported in Testosterone Trial in Older Men. National Institutes of Health. June 30, 2010.  Budoff MJ, Ellenberg SS, et. al. Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone. JAMA. 2017 Feb 21;317(7):708-716. PMID: 28241355

Researchers identify gene
tied to neural-tube defects

BALTIMORE – A gene has been identified that triggers a process leading to the formation of neural-tube defects (NTDs) commonly found in infants of pregnant women with diabetes, according to recent research.

This is the first time the gene has been shown to play this role, according to the study published in May in Nature Communications.

Its authors---including Fang Wang and Cheng Xu, who are affiliated with the University of Maryland School of Medicine, Baltimore---report that the identification of this gene opens up a new way to understand these defects and that their work may lead to new treatments that could prevent the problem or decrease its incidence.

The researchers note that even small, brief spikes in a pregnant woman’s blood-glucose level can spur diabetes-associated birth defects, and that even women who monitor and control blood sugar are at greater risk of having a baby with NTDs than those without the disease.

Since this developmental process takes place very early in pregnancy---often before the woman knows she is expecting---by the time pregnancy is confirmed, damage from elevated blood glucose to the developing central nervous system (CNS) may already have occurred.

The authors focused on a gene called Prkca, which plays a vital role in regulating autophagy…the process through which cells dispose of un-needed material, which is often broken or flawed.

In diabetes, the Prkca gene becomes over-active; as a result, autophagy is suppressed, and the flawed cellular material is used to create embryonic tissue that can lead to major birth defects.

CITATION: Fang Wang, Cheng Xu, et. al. Protein kinase C-alpha suppresses autophagy and induces neural tube defects via miR-129-2 in diabetic pregnancy. Nature Communications 8, Article number: 15182 (2017) Received: 07 July 2016. Accepted: 03 Marcg 2017. Published online: 05 May 2017.
University of Maryland School of Medicine researchers identify gene that controls birth defect common in diabetes.  University of Maryland School of Medicine.

Body-fat measures supported
for kidney-function estimates

MEXICO CITY – Anthropometric measures of body fat appear to provide equally-consistent estimates of kidney-function (KF) decline risk as computed tomography (CT) measures in elders, according to a study published in May in the Clinical Journal of the American Society of Nephrology.

Its authors---including Magdalena Madero, of the Instituto Nacional de Cardiología Ignacio Chávez, Mexico City---noted that while anthropometric body-fat measures are associated with chronic-kidney disease (CKD) development, they may be less accurate than CT measures.

The researchers compared the association of CT and anthropometric measures of obesity with kidney outcomes in the Health Aging and Body Composition Study.

Participants were recruited from March, 1997, through July, 1998. CT measures included:
visceral abdominal fat (VAT); subcutaneous adipose tissue (SAT); and inter-muscular fat area (IMAT).

 Anthropometric measures included: waist circumference (WC); and body mass index (BMI).

Kidney outcomes included KF decline or incident CKD.

Two-thousand four-hundred and eighty-nine subjects were included. Mean age was 74 (plus-or-minus three years); 49% were men, 39% were black, 59% were hypertensive, and 15% were diabetic.

KF decline occurred in 17% of the population, and incident CKD occurred in 17% of those at risk.

In continuous models, SAT, VAT, IMAT, BMI, and WC (per SD increase) were all significantly associated with KF decline.

There was a significant interaction between VAT and CKD with regard to KF decline.
Only VAT, BMI, and WC were associated with incident CKD, and only VAT remained a significant risk factor for incident CKD when other exposure variables were included in the same model.

There was no association between any measure of obesity and kidney outcomes when creatinine values at years three and 10 were used to estimate changes in estimated glomerular filtration rate (eGFR).

CITATION: Magdalena Madero, Ronit Katz, et. al.  Comparison between Different Measures of Body Fat with Kidney Function Decline and Incident CKD.  Clinical Journal of the American Society of Nephrology. May 2017. Received July 6, 2016. Accepted March 1, 2017 Published online before print, May 2017.

Study: Weight-loss intervention
won't preferentially target VAT

MILAN – A review published recently in the International Journal of Obesity concludes that there is no evidence of a weight-loss intervention (lifestyle modification, weight-loss promoting drugs, bariatric surgery) that preferentially targets visceral adipose tissue (VAT).

Authors of the research published in March---including Claudia Meriotti, who is affiliated with the Universita degli Studi di Milana, Milan---also indicate that basal VAT depots are smaller than basal subcutaneous adipose tissue (SAT) depots, and that VAT loss is linked to SAT loss.
Only percent VAT loss is greater than percent SAT loss; this applies to all strategies.

The researchers also note that there are no shortcuts to losing VAT through the available strategies.
This suggests that VAT, while more dangerous, is also more vulnerable than subcutaneous fat. This finding could spur deeper studies of the biology of VAT and hopefully lead to more specific targets for VAT reduction.

The authors analyzed 89 studies in their evaluations of visceral and subcutaneous fat changes, measured through ultrasound, computerized tomography, magnetic resonance imaging (MRS) and expressed as thickness, weight, area and volume.

They found that: subcutaneous fat was greater than visceral fat when measured as area, volume and weight, but not as thickness;  decrease of subcutaneous fat was greater than visceral fat when measured as area, volume and weight, though not as thickness; and that percent decrease of visceral fat was always greater than percent decrease of subcutaneous fat, with no differences between different strategies.

No intervention preferentially targets visceral fat, and basal visceral fat depots are smaller than basal subcutaneous fat depots.

Visceral fat loss is linked to subcutaneous fat loss, and, with all strategies, percent decrease of visceral fat prevails over subcutaneous fat loss.

CITATION: C Merlotti, V Ceriani, et. al. Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis. International Journal of Obesity (2017) 41, 672-682; published online 7 March 2017. Received 28 July 2016; Revised 30 December 2016. Accepted 20 January 2017. Accepted article preview online 2 February 2017; Advanced online publication 7 March 2017.

Vitamin D repletion is associated
with decreased disease activity

BOSTON – Vitamin D repletion is associated with decreased disease activity and increased quality of life (QOL) in Crohn’s disease (CD), according to a study published in May in Digestive Diseases and Sciences.

Its authors---including Samantha Zullow, Boston University School of Medicine, Boston---also indicate that in a tertiary-care inflammatory bowel disease (IBD) cohort, most patients have low vitamin D levels, and that non-Caucasian race and female gender are associated with low vitamin D.

The researchers also indicate that ulcerative colitis (UC) is associated with lower risk of vitamin D insufficiency.

Noting that many IBD patients are vitamin D deficient, the authors set out to identify risk factors for vitamin D deficiency in IBD and assess the impact of vitamin D repletion on disease activity and QOL.

The researchers evaluated patients with at least one 25-OH vitamin D level measured between 2004 and 2011; those with levels of less than 30 ng/ml at baseline were followed until time of repletion.
QOL and disease-activity scores were measured at baseline and repletion.

Two-hundred-and-fifty-five patients were identified; 33%, 29%, and 39% had vitamin D levels of at least 30, 20-to-29, and less than 20 ng/ml, respectively.

When adjusting for disease type and duration, gender, smoking, and race, non-Caucasians had 5.3 and UC patients 0.59 odds of having vitamin D of less than 30 ng/ml.
Women were 1.7 times more likely to have a 25-OH vitamin D level of less than 20 ng/ml than men; 55 patients underwent repletion.

CITATION: Zullow S, Jambaulikar G, et. al. Risk Factors for Vitamin D Deficiency and Impact of Repletion in a Tertiary Care Inflammatory Bowel Disease Population. Dig Dis Sci. 2017 May 25. [Epub ahead of print] PMID: 28547646.

Child-obesity treatments addressed
in study included in Clinician Reviews

An article in the Clinical Edge section of June's Clinician Reviews addresses the question of whether children need to be present during obesity treatments. Quoting from a study published in May in JAMA Pediatrics, the article notes that, in treatment for child-weight loss, parent-based (parent-only) treatment was as effective as family-based (parent-and-child) treatment. The study assessed 150 overweight-and-obese eight-to-12-year-old children and their parents. The article can be accessed at


Vol. 3 No. 16

Goal-directed treatment backed

as ’next level’ for osteoporosis

SOUTHBURY, CONN. – An expert on osteoporosis says the goal-directed treatment approach presented in a recent report may boost care "to the next level" following what he calls a "decline" in attention to the disease.

Rick Pope, physician assistant (PA)-C, Department of Rheumatology, Western Connecticut Medical Group, Danbury, Conn., has high hopes for the efforts of the working group formed by the American Society for Bone and Mineral Research (ASMBR) and the United States National Osteoporosis Foundation (NOF).

The group’s progress report published in December by the Journal of Bone and Mineral Research defines goal-directed treatment as a strategy in which:

  • treatment goals are established for patients
  • initial treatment choices are based on the probability of reaching goals
  • progress towards reaching goals is reassessed periodically
  • the overriding treatment goal is to achieve freedom from fracture or at least low-fracture risk

Treatment goals include:

  • t-scores of more than minus 2.5
  • achievement of an estimated risk level below the threshold for initiating treatment

Pope, a Southbury, Conn., resident, founder and past three-time president of the Society of Physician Assistants in Rheumatology (SPAR), and faculty member of the Metabolic & Endocrine Disease Summit (MEDS), points to expectations for two drugs that could hit the market this year as among his reasons for optimism.

One, from Radius Health, is abaloparatide-SC 80 mcg, an investigational, once-daily treatment for post-menopausal women with osteoporosis; if approved by the U.S. Federal Drug Administration (FDA), it would be the first new bone-anabolic treatment option in the U.S. since 2002 for post-menopausal women with osteoporosis; a New Drug Application (NDA) was submitted last year.

Also: Amgen and UCB last year announced that the FDA accepted for review the Biologics License Application (BLA) for romosozumab, an investigational monoclonal antibody for the treatment of osteoporosis in post-menopausal women at increased risk of fracture. Romosozumab---for which the FDA has set a Prescription Drug User Fee Act (PDUFA) target-action date of July 19---works by binding and inhibiting the activity of the protein sclerostin, a protein naturally occurring in the bone, thereby increasing bone formation and decreasing bone resorption.

"The recommendations in this [working-group] report," says Pope, "would make goals more targeted, with levels of osteoporosis treatment based on bone mineral density (BMD). The report can make significant headway in treatments and approaches that are user-friendly, especially for primary care."

The report notes that goal-directed treatment can’t be fully achieved without medications that provide greater BMD increases and greater fracture-risk reductions.

Pope says a goal-directed approach will benefit patients of PAs and nurse practitioners (NPs) once the new approach becomes a reality, possibly during the next three years.

"The direction," he says "is to give practitioners a more specific end-point for management. The patient is directed to a number on a bone-density machine. With that goal in mind treatment is started or a change in treatment is recommended. It will be easier to set and reach goals in many cases, which is not currently being done, as goals are fuzzy, and BMD maintenance and some measure of improvement is recommended."


The report, Pope says, "is driven by data from studies, using large meta-data analysis to come up with conclusions. Meta-data analysis can be tricky. Studies are done with different end-points and populations, and conclusions may not be as specific as we like."


Pope echoes the report’s cautionary note that treatment selection is often based on or constrained by payer-reimbursement policies.


"Costs," he says, "will be closely calculated by insurance companies, and numbers needed to prevent fractures will be carefully estimated. If patients undertake any form of therapy, overall benefits will need to be shown as compared to the cost of care for hip fractures, spinal fractures and other incident fractures. An arduous task."


He underscores this emphasis by noting that "the most-costly, and most deadly, fracture is the hip fracture."


A goal-directed approach, Pope concludes, "can take osteoporosis treatment to the next level, getting to goals that will be verified and validated with newer and more potent medications that will be achievable for most."


"This is a large undertaking," he says, "and I applaud it. It will and should go this next step however better pharmaceuticals and more aggressive regimens are needed to make an important and recognizable difference in the osteoporosis population."

CITATION: Steven R. Cummings, Felicia Cosman, et. al. Goal-Directed Treatment for Osteoporosis: A Progress Report From the ASBMR-NOF Working Group on Goal-Directed Treatment for Osteoporosis. Journal of Bone and Mineral Research. First published 27 December 2016. Volume 32, Issue 1. January 2017. Pages 3-10.

Diabetic retinopathy targeted

in recommendations from ADA

BALTIMORE – A recent American Diabetes Association (ADA) position statement cites studies showing the positive effects tight glycemic control can have on diabetic retinopathy risks and progressions in patients with diabetes, and how those benefits can last for years.

The statement published in March in Diabetes Care outlines the stages of diabetic retinopathy and highlights recommendations on optimal blood-glycemic control and lowering blood pressure.

Its authors---including Sharon D. Solomon, Johns Hopkins Medicine, Baltimore, and Emily Chew, National Institutes of Health, Bethesda, Md.---also include screening recommendations suggesting that adults with type 1 diabetes receive comprehensive eye exams within five years of the onset of diabetes, and that those with type 2 diabetes have exams at time of diagnosis.

If there is no evidence of retinopathy for one or more annual eye exams, the statement indicates, exams every two years may be considered.

They also recommend that women with pre-existing type 1 or type 2 diabetes who are pregnant or planning to become pregnant be counseled on the risks of development and/or progression of diabetic retinopathy.

If any level of diabetic retinopathy is present, subsequent dilated retinal examinations for patients with type 1 or type 2 diabetes should be repeated at least annually by an ophthalmologist or optometrist; if retinopathy is progressing or sight-threatening, examinations will be required more frequently.

Treatment recommendations include:

  • prompt referral of patients with any level of macular edema; severe non-proliferative diabetic retinopathy (a precursor of proliferative diabetic retinopathy); or any proliferative diabetic retinopathy to an ophthalmologist who is knowledgeable and experienced in management and treatment of diabetic retinopathy
  • laser photocoagulation therapy reduces vision-loss risk in patients with high-risk proliferative diabetic retinopathy and, in some cases, severe non-proliferative diabetic retinopathy
  • intravitreous injections of anti-vascular endothelial growth factor are indicated for central-involved diabetic macular edema (DME)
  • while optimization of blood glucose, blood pressure, and serum lipid levels in conjunction with dilated eye examinations can substantially decrease the vision-loss risk from complications of diabetic retinopathy, a significant proportion of those affected with diabetes develop DME or proliferative changes requiring intervention


CITATION: Sharon D. Solomon, Emily Chew, et. al. Diabetic Retinopathy: A Position Statement by the American Diabetes Association. Diabetes Care. March 2017.

Research: High-protein diet won’t

significantly affect FFM changes

AMSTERDAM – A high-protein diet, though lower than targeted, does not significantly affect changes in fat-free mass (FFM) during modest weight loss in older overweight and obese adults, according to a study published in February in the Nutrition Journal.

Its authors---including Amely M. Verreijen and Mariélle F. Engberink, Amsterdam University of Applied Sciences, Amsterdam---also indicate that there is no significant interaction between the high-protein diet and resistance exercise for change in FFM.

The researchers, who investigated whether a high-protein diet and/or resistance exercise preserves FFM during weight loss among overweight and obese adults, determined that only the studied group with a combined intervention of high-protein diet and resistance exercise significantly increased in FFM.

This suggests that combining protein with resistance exercise is beneficial for FFM preservation during weight loss for older adults; the researchers add that this point should be confirmed by future studies using a larger protein contrast.

The authors, noting that intentional weight loss in older obese adults is a risk factor for accelerated muscle-mass loss, assessed 100 overweight and obese adults, aged 55-to-80 years-of-age, in a randomized controlled trial (RCT) with a two-by-two factorial design and intention-to-treat analysis.

All subjects followed a hypocaloric diet during a 10-week weight-loss program; subjects were randomly allocated to either a high- or normal-protein diet, with-or-without a resistance-exercise program three times a week. FFM was assessed by air-displacement plethysmography.

Both high-protein diet and exercise did not significantly affect change in body weight, FFM and fat mass (FM).

No significant protein-exercise interaction effect was observed for FFM, although within-group analysis showed that high protein in combination with exercise significantly increased FFM.

Also: A March research letter in the Journal of American Medicine reports on a study of adults who were overweight or obese and trying to lose weight during three periods from 1988 through 2014. The letter---which can be accessed at that a growing number of such adults are not trying to loss excess weight.

CITATION: Amely M. Verreijen, Mariélle F. Engberink, et. al. Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Nutrition Journal. Received: 19 October 2016. Accepted: 16 January 2017. Published: 6 February 2017.

Novel assay targets benign,

malignant thyroid nodules

REHOVOT, ISRAEL – A novel assay utilizing microRNA expression in cytology smears is the subject of benign-and-malignant thyroid-nodule research published in February in the Journal of Clinical Pathology.

Its authors---including Gila Lithwick-and Nir Dromi, of Rosetta Genomics Ltd., Rehovot, Israel---note that the assay distinguishes benign from malignant thyroid nodules using a single fine-needle aspirate (FNA)-stained smear, and does not require fresh tissue or special collection-and-shipment conditions.

The assay offers a tool for the pre-operative classification of thyroid samples with indeterminate cytology.

The researchers present a new diagnostic assay and evaluate its performance on a blinded set of 189 samples from several sources.

The test described in the paper is a multi-center, clinically-evaluated, commercially-available assay that can accurately differentiate between malignant-and-benign thyroid nodules using routinely-prepared FNA-stained smears.

A training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated with a blinded, multi-center, retrospective cohort of 201 smears.

Validation samples were from adult patients at least 18 years of age with nodule sizes of more than 0.5 cm, and a final diagnosis confirmed by at least one of two blinded, independent pathologists.

Take-home messages include:

  • 10%-to-40% of thyroid FNAs are not conclusively diagnosed by cytology and are categorized as indeterminate
  • the RosettaGX Reveal assay, which was blindly validated, differentiates benign from malignant thyroid nodules in indeterminate smears
  • smear used for the assay can be a routinely-prepared smear used to make the indeterminate diagnosis, and does not require a repeat FNA
  • the assay does not require fresh tissue or special collection and shipment conditions
CITATION: Gila Lithwick-Yanai, Nir Dromi, et. al. Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears. Journal of Clinical Pathology. 02/06/2017.;
Harmonized-reference ranges

are assessed for testosterone

BOSTON – A recent study indicates that a substantial proportion of inter-cohort variation in testosterone levels is due to assay differences.

Data in the study published in January in The Journal of Clinical Endocrinology & Metabolism demonstrates the feasibility of generating harmonized-reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.

The study---whose authors include Thomas G. Travison, Harvard Medical School, Boston, and Hubert W. Vesper, Centers for Disease Control and Prevention, Atlanta---indicates that the harmonized-normal range in the non-obese population of European and American men aged 19-to-39 years is 264-to-916 ng/dL.

The researchers note that reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men and set out to establish harmonized-reference ranges for total testosterone that can be applied across laboratories by cross-calibrating cohort-specific assays to a reference method and standard.

The research included 9,054 community-dwelling men in cohort studies in the United States and Europe from: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; Male Sibling Study of Osteoporosis.

Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method from the Centers for Disease Control (CDC). Generalized-additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values.

And in a related matter: An editorial published in February by the Journal of the American Medical Association assesses testosterone and male aging. It can be accessed at

CITATION: Thomas G. Travison, Hubert W. Vesper, et. al. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the USA and Europe. The Journal of Clinical Endocrinology & Metabolism. Published: 10 January 2017.
Clinician Reviews addresses

issue of vitamin D’s role in MS

A March article in Clinician Reviews assesses the role of vitamin D in multiple sclerosis (MS). Written by Lisa Marie Fox, MSPAS, PA-C, who is affiliated with Johns Hopkins Hospital in Baltimore, the piece notes that living farther from the equator, not being exposed to sunlight, and having a low vitamin D level are correlated with increased risk for MS and MS relapse. The article---which can be accessed at that, in light of the anti-inflammatory effects of vitamin D and its purported reduction of MS risk, it is possible that MS patients should start vitamin D supplementation early in order to obtain maximum anti-inflammatory effects.


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