Articles

2018 Cholesterol Guidelines: Key Points

2018 Cholesterol Guidelines: Key Points

Cardiovascular disease is the leading cause of death in the United States. Cholesterol anomaly, or dyslipidemia, is a major contributor to atherosclerosis morbidity and mortality. Multi-society new cholesterol guidelines were recently published. They were contributed and endorsed by ACC, AHA, ADA, and NLA, among other national associations. You can find below the key recommendations published in the journal of Circulation, November 2018.

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New FDA approval: retacrit, to improve anemia of kidney disease

New FDA approval: retacrit, to improve anemia of kidney disease

Erythropoietin is a key hormone produced by the kidney to stimulate bone marrow production of red blood cells. FDA has now approved the second erythropoietin analog, retacrit, in addition to epogen. It shows similar efficacy and side effects to epogen. This approval allows both medications to be more accessible to patients, at a lower cost. It is indicated for treatment of anemia of chronic kidney disease or from use of chemotherapy and zidovudine. It could also be used preemptively prior to surgeries with expected major blood loss.

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Sexual function after bariatric surgery

Sexual function after bariatric surgery

This meta-analysis shows that bariatric surgery significantly improves sexual function in men but that a more limited degree of improvement is achieved in women.

In obese male patients who underwent bariatric surgery, the levels of the sex hormones TT, FT, LH, FSH, and SHBG significantly increased, and the level of E2 decreased. In obese female patients, the levels of the sex hormones TT, FT, and E2 decreased, but the levels of LH, FSH, and SHBG increased.

Future studies should be performed to elucidate the mechanism of the improved sexual function in obese patients after bariatric surgery. 

JES

Early heart disease in diabetes and prediabetes

Early heart disease in diabetes and prediabetes

The study finds that the longer the duration of diabetes and prediabetes in early adulthood, the higher the risk of progressive subclinical atherosclerosis and cardiac pump dysfunction, in both phases of contractility and relaxation. About 3,600 patients of age 18-30 were followed for 25 years. This is yet another reason to screen and intervene aggressively young individuals for both prediabetes and diabetes.

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Right adrenal tumors are frequently missed

Right adrenal tumors are frequently missed

A serious article analyzing the prevalence of left-sided vs. right-sided adrenal tumors. Prior observations have consistently shown that left-sided adenomas are more common than right-sided ones, in 2:1 ratio.

Although a reason could be embryological, leading to a greater left adrenal vascularity, innervation, volume and mass; authors suggest that asymmetry could also be due to anatomical locations of the glands.

The left adrenal gland is surrounded by the hypo-attenuated visceral fat, making it easier to be seen by imaging, versus the right gland which is somewhat compressed by the relatively hyper-attenuated liver and kidney.

Authors' argument is compelling enough that clinicians should be aware of possibly missing right-sided adrenal tumors, especially in the context of hyper-functionality; elevated catecholamines, cortisol, aldosterone and DHEAs.

GT

Differentiating LADA, type 1 and type 2 diabetes

Differentiating LADA, type 1 and type 2 diabetes

It is not always easy to distinguish LADA from type 1 or type 2 diabetes. Common parameters utilized are BMI, age, family history, HLA-typing, clinical presentation, glucose variability and severity, insulin production, C-peptide levels, as well as autoantibodies against glutamic acid decarboxylase (GAD65), pancreatic islet cells (ICA) or insulin (IAA).

The article shows that other inflammatory markers could also be useful in differentiating the diagnoses. Such markers are; adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNFR2), interleukin-6 (IL-6), hs-CRP, and total leukocyte number. More research is needed on how to incorporate the additional tests in clinical practice.

GT

Late-night salivary cortisol measurements are not consistent in cushing disease

Late-night salivary cortisol measurements are not consistent in cushing disease

The study reveals that late-night salivary cortisol (LNSC) measures are variable in cushing disease, particularly in those with recurrent or persistent illness. Less variability was seen in new cases of the disease who had not undergone treatment. Hypercortisolemia is expected to be lower in treated vs. untreated patients, thus it is reasonable to suspect similar inconsistencies in LNSC values in those with subtle hypercortisolemia, frequently seen with adrenal adenomas.

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New FDA approval: drug therapy for anaplastic thyroid cancer

New FDA approval: drug therapy for anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid cancer. It accounts for about 1-2% of all thyroid cancers. NIH estimates 54,000 new cases of thyroid cancer and 2,000 deaths from the disease in the US in 2018. 

The tafinlar + mekinist combination is now approved for the treatment of BRAF V600E mutation-positive ATC that cannot be addressed surgically or has already spread to other organs. Tafinlar and Mekinist have also been approved for two other BRAF V600 mutation-positive metastatic malignancies; melanoma and non-small cell lung cancer.

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A possible new drug for diabetes and obesity (PTP1b inhibitor)

A possible new drug for diabetes and obesity (PTP1b inhibitor)

Protein tyrosine phosphatase 1B (PTP1b) was first discovered in 1988. It is a counter-regulator to insulin and leptin signaling pathways. Given current endemic of insulin resistance via obesity and type 2 diabetes, it is natural to search for drugs that improve insulin and leptin sensitivities. PTP1b suppression is one of those options.

Here is a phase 2 clinical trial on an antisense inhibition of PTP1b (IONIS-PTP-1BRx). Results are promising but not profound: A1c and body weight dropped by 0.7% and 6 lbs in 27 to 36 weeks. No major adverse events were seen. A clearer picture of the drug will emerge in the future trials. At the same time the search for the other perfect PTP1b continues.

GT

The semi-automated insulin pump performs well

The semi-automated insulin pump performs well

The study reveals that the hybrid closed loop device, MiniMed 670g, helps in reducing A1c by 0.75% compared to standard insulin pumps. For those transitioning to it, carbohydrate to insulin ratio needs to be adjusted immediately. This semi-automated system, differently called semi-artificial pancreas, is a significant advancement in the field of type 1 diabetes. The device was approved by FDA in September 2016.

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Leptin improves brain insulin resistance

Leptin improves brain insulin resistance

Leptin deficiency leads to weight gain, obesity, and insulin resistance. Leptin replacement in the form of metreleptin has been approved by the FDA for congenital or acquired generalized lipodystrophy. The current analysis reveals that metreleptin also improves central insulin sensitivity primarily via hypothalamus and to a lesser extent prefrontal cortex.

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Review of 2018 ADA guidelines: dyslipidemia in the context of diabetes

Review of 2018 ADA guidelines: dyslipidemia in the context of diabetes

ADA recommendations are released each January. Below is a succinct ACP review of guidelines in screening, treatment goals, lifestyle intervention, and drug approach to dyslipidemia in the setting of diabetes mellitus. LDL-cholesterol is still a main target. Charts depict indications and doses of statins, the mainstay therapy to diabetic lipid disorders.

GT

A rare source of cushing's syndrome: ovary

A rare source of cushing's syndrome: ovary

Cushing's syndrome (CS) is a rare illness that leads to visceral adiposity, muscle wasting, insulin resistance, osteoporosis, diabetes, blood clots, high blood pressure, dyslipidemia and frequent infections. Subsequently, affected individuals have increased mortality rates.

The most common cause of the syndrome is a pituitary tumor, otherwise called cushing disease. Although rare, other organs also have the potential of producing excessive cortisol. The article describes a unique case of CS where the source is a right ovarian mass. The selective ovarian and adrenal venous sampling was important in confirming the diagnosis, and eventually driving the therapy.

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Phosphorous balance in chronic kidney disease

Phosphorous balance in chronic kidney disease

In the setting of chronic kidney disease, elevated blood phosphorous levels can increase the risk of death, in addition to cardiovascular, parathyroid and bone disorders. This case shows us that the other extreme is also dangerous: severe oral phosphorous restriction and severe hypophosphatemia lead to profound muscle weakness, ostemalacia, osteoporosis and multiple bone fractures. Arisotle's aurea mediocritas applies nicely here too.

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Less vitamin D, more diabetes

Less vitamin D, more diabetes

This prospective cohort study reveals an inverse relationship between blood vitamin D25 levels and risk of diabetes. Future research will show if this connection is causative in nature. Certainly there is some physiological and pathophysiological explanation: pancreatic beta cells are known to have vitamin D receptors, that upon VitD metabolites stimulation they produce and release insulin. Secondly, low vitamin d is also a proinflammatory state, an independent risk factor for diabetes development. 

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Night shift work is associated with a higher risk of diabetes

Night shift work is associated with a higher risk of diabetes

Circadian rhythm and cortisol dysregulations have been associated with higher predisposition toward development of diabetes, obesity and metabolic syndrome. Subsequently it is of no surprise that night shift work, a form of circadian and cortisol anomaly, is also shown to raise the risk of diabetes mellitus.

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New FDA approval: a more convenient test for adult growth hormone deficiency

New FDA approval: a more convenient test for adult growth hormone deficiency

FDA has approved the oral agent macrilen for evaluation of growth hormone deficiency in adults. Macrilen is a ghrelin agonist which leads to the provocative release of growth hormone by the anterior pituitary gland. The diagnostic procedure is safe, efficient and comparable with the gold standard isulin tolerance test (ITT). This is a meaningful advancement in the field of endocrinology.

GT

A case of nephrogenic diabetes insipidus

A case of nephrogenic diabetes insipidus

Although uncommon, lithium can cause endocrinopathies such as hypothyroidism, hyperthyroidism, hyperparathyroidism, and diabetes insipidus. Diabetes insipidus (DI) is of nephrogenic source, resulting in tubulointerstitial anomaly and resistance to vasopressin. 

Vasopressin or ADH is produced in the hypothalamus but released by the posterior pituitary gland. It is responsible for retaining free water by the kidneys. Nephrogenic DI can lead to increased urination and high blood sodium levels.

This case shows a nice correspondence between lithium-induced renal pathoanatomy and pathophysiolgy.

GT

Stop puberty obesity!

Stop puberty obesity!

This is a nice epidemiological study of childhood overweight and obesity as it pertains to development of type 2 diabetes in adulthood. Authors have observed that heavy children who are no longer overweight after age 13 are not at increased risk of diabetes as adults. On the contrary, the longer the duration of high BMI during puberty, the higher the probability of developing early diabetes mellitus.

GT

New FDA approval: artificial intelligence for diabetic eye disease.

New FDA approval: artificial intelligence for diabetic eye disease.

Diabetic retinopathy occurs when high levels of blood sugar lead to damage in the blood vessels of the retina, the light-sensitive tissue in the back of the eye. Diabetic retinopathy is the most common cause of vision loss among the more than 30 million Americans living with diabetes and the leading cause of vision impairment and blindness among working-age adults.

FDA