Children

A great prospect for type 1 diabetes

A great prospect for type 1 diabetes

Type 1 diabetes is a devastating life-long condition. It is autoimmune and frequently occurs in predisposed young adults. Chronic therapy is insulin use via multiple daily injections or insulin-pump; in addition to intensive lifestyle modifications.

The best management of type 1 diabetes is proactive prevention or elimination rather than reactive insulin usage. The current study addresses this very point. A group of 76 participants at high-risk for DM1 was randomized to receive teplizumab or placebo. The presence of autoantibodies to various entities such as GAD65, MicroIns, IA2, ICA, and ZnT8 defined the high-risk status.

Investigators followed subjects for six years. Remarkably at any point in time; teplizumab prevented the development of type 1 diabetes by about 60%. The annual rate of diagnosed diabetes was 16% vs. 39% in those treated with and without teplizumab.

Teplizumab is an immune modulator via CD3 co-receptor pathway. Treated patients experienced a higher rate of adverse events in the form of rash and temporary reduction in lymphocyte count.

I anticipate that further intense research on the subject will yield even higher rates of prevention in predisposed individuals. Family history and biochemical screening of patients would be parament. Stay tuned for similar research results as the DM1-prevention space is blossoming.

GT

Victoza use in children with diabetes type 2

Victoza use in children with diabetes type 2

Results of ELLIPSE trial are of major significance as they show that Victoza addition to Metformin helps in further reduction of A1c and fasting plasma glucose. The efficacy and safety appear to be similar as in adults. The most common side effects are gastrointestinal in nature. Based on ELLIPSE trial outcomes, I anticipate broadening of FDA indications for Victoza, to include children and adolescents

GT

Pituitary enlargement due to hypothyroidism

Pituitary enlargement due to hypothyroidism

Another nice report of total pituitary enlargement due to the long-standing untreated primary hypothyroidism. Low levels of FT3 and FT4 lead to excessive TRH and TSH production, in turn causing pituitary expansion.

This case is unique as it is found in a child suffering from growth retardation. Proper treatment with thyroid hormone supplementation reversed the illness.

GT

Novel Approach: Verapamil for Type 1 Diabetes

Novel Approach: Verapamil for Type 1 Diabetes

Old drug, new approach. Verapamil has classically been used to treat hypertension and cardiac arrhythmias. This randomized phase 2 clinical trial shows a novel use of the drug by improving pancreatic beta cell function in recently diagnosed type 1 diabetes. Verapamil helped patients use lower doses of insulin as well as experiencing less hypoglycemia. These are exciting and promising results.

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: the first drug for x-linked hypophosphatemia

New FDA approval: the first drug for x-linked hypophosphatemia

Crysvita or burosumab is the first drug to be approved by FDA for treatment of x-linked hypophosphatemia in adults and children older than one year of age. It is inherited, rare and unresponsive to vitamin D supplementation. It is a form of ricket and osteomalacia leading to low blood phosphorus levels.  Clinical manifestations are disabled bone growth and development in children and impaired bone mineralization in adults.

GT

Trends of kidney disease in children with type 1 diabetes

Trends of kidney disease in children with type 1 diabetes

This observational study reveals important long-term trends of type 1 diabetes in regard to kidney function & end stage renal disease (ESRD). Subjects were followed for up to 42 years:

Rates of ESRD are lower when children are diagnosed with DM1 before age 10 than during puberty. Kidney disease is less prevalent in females than males. Diabetic nephropathy peaks at 25 years after diagnosis and remains stable subsequently.

These findings could be shared with parents at the time of child's type 1 diabetes diagnosis.

GT

Albumin excretion during puberty in the setting of type 1 diabetes.

Albumin excretion during puberty in the setting of type 1 diabetes.

The use of an ACE inhibitor and a statin did not change the albumin-to-creatinine ratio over time among adolescents with type 1 diabetes. Neither drug had significant effects on carotid intima–media thickness, other cardiovascular markers, the glomerular filtration rate, or progression of retinopathy.

NEJM

FDA label change: opioid ingredients in children

FDA label change: opioid ingredients in children

The U.S. FDA announced today that it is requiring safety labeling changes to limit the use of prescription opioid cough and cold medicines containing codeine or hydrocodone in children younger than 18 years old because the serious risks of these medicines outweigh their potential benefits in this population. After safety labeling changes are made, these products will no longer be indicated for use to treat cough in any pediatric population and will be labeled for use only in adults aged 18 years and older.

FDA

Obesity, from childhood to adulthood

Obesity, from childhood to adulthood

The study predicts dim outcomes. Around 57% of today's children are expected to be obese by age 35. High BMI and particularly high waist circumference are well known contributors to inflammation, insulin resistance, diabetes, high blood pressure, metabolic syndrome and malignancy.

Can it be delayed, reversed, stopped? If so, how? Education?

GT

How to look for monogenic diabetes

How to look for monogenic diabetes

Authors propose an efficient and simple way to screen for monogenic diabetes. All individuals, diagnosed with type 1 diabetes before age 30, should be tested for serum or urinary C-peptide levels. If C-peptide is present then GAD and IA1 antibodies are measured.  If antibodies are undetectable, then patients should undergo genetic testing.

This simple protocol has a 20% chance of identifying monogenic diabetes. In other words, it improves positive predictive value from baseline 3.6% to 20%, with an impressive negative predictive value 99.9%. Identifying this rare form of diabetes is important, as patients could switch from insulin to oral sulfonylurea. In addition, family members could benefit from genetic screening and counseling. 

GT

Thyroid-cholesterol axis in overweight children

Thyroid-cholesterol axis in overweight children

A group of 330 overweight or obese children, without thyroid anomalies, were followed for TSH, free T4 versus CVD identifiers; total cholesterol (TChol), LDL-cholesterol (LDL), triacylglycerol (TAG), and monocyte chemotactic protein 1 (MCP1).

Tests were measured before and after one year of lifestyle intervention, including weight loss. Study finds that TSH, but not free T4, correlates positively with CVD markers, suggesting direct involvement of TSH in lipoprotein metabolism.

It is speculated that TSH receptors, present in hepatocytes, are responsible for direct cholesterol synthesis and lower bile acid production under TSH stimulation. Future studies could address interventional outcomes of thyroid hormone on TSH and CVD risk factors.

GT

Monogenic diabetes, more common than we think

Monogenic diabetes, more common than we think

Authors found that prevalence of monogenic diabetes was higher at 6.3% then previously estimated among pediatric population (number one cause being diabetes type 1). MODY composed majority 87% of these cases. Proper genetic diagnosis is important as some children could be treated with sulfonyluria rather then daily insulin injections.

GT

Children, Lipodystrophy and Leptin

Children, Lipodystrophy and Leptin

Lipodystrophy (LD) could be familial or acquired, partial or generalized. This original NIH study shows that metreleptin, a leptin analog, can nicely improve LD metabolic anomalies; such as high glucose, triglycerides and liver enzymes. These benefits are expected to decrease long-term lipodystrophy complications in young individuals.

GT

Would Growth Hormone Treatment Lead to Cancer?

Would Growth Hormone Treatment Lead to Cancer?

The study raises concern for possible new cancer development in patients treated with human growth hormone, while already having a history of treated malignancy. There was also a trend for Hodgkin lymphoma, bone and bladder cancer in individuals without prior history of carcinoma. About 25,000 patient data were analyzed, including initial hGH users from 1984. Further research is needed to confirm or identify the mechanism of causality.

GT

Long-acting Human Growth Hormone

Long-acting Human Growth Hormone

Long acting human growth hormone, now in a phase 2 trial, appears to be efficacious and tolerable. Its duration of action is about 5-10 times longer then the daily-dose counterpart. It is administered once weekly and so it could improve adherence to therapy in children.

GT

2017 Guidelines: Pediatric Obesity

2017 Guidelines: Pediatric Obesity

"Pediatric obesity remains an ongoing serious international health concern affecting ∼17% of US children and adolescents, threatening their adult health and longevity. Pediatric obesity has its basis in genetic susceptibilities influenced by a permissive environment starting in utero and extending through childhood and adolescence.

Endocrine etiologies for obesity are rare and usually are accompanied by attenuated growth patterns. Pediatric comorbidities are common and long-term health complications often result; screening for comorbidities of obesity should be applied in a hierarchal, logical manner for early identification before more serious complications result.

Genetic screening for rare syndromes is indicated only in the presence of specific historical or physical features. The psychological toll of pediatric obesity on the individual and family necessitates screening for mental health issues and counseling as indicated."

J C E M

Homozygous familial hypercholesterolemia: LDL Apheresis

Homozygous familial hypercholesterolemia: LDL Apheresis

Homozygous familial hypercholesterolemia results from full deficiency of malfunction of LDL receptors in the liver. Risk of coronary artery disease is skyrocketed. It is often hard to treat with statin-based combination therapy. Lipoprotein apheresis could be the only hope for affected individuals.

Please find below a nice case study of LDL-apheresis effectiveness in 3 siblings. Twice weekly session with 1.5 exchange volume brought LDL-C to target without any noticeable adverse events.

GT