Obesity

Hypoglycemia due to gastric bypass surgery

Hypoglycemia due to gastric bypass surgery

Obesity and its complications are common, yet on the rise. Subsequently, gastric bypass surgery is on the rise too. Severe hypoglycemia can be a long-term complication of bariatric surgery. The most common method to negate or reduce hypoglycemia is dietary modifications. Patients need to consume small meals of a low glycemic index frequently. Medical therapies with acarbose, diazoxide, and octreotide are often not useful.

Here authors describe the utility of calcium channel blockers (CCBs) in two patients. Difficult to treat hypoglycemia developed in 8 and 13 years after the bypass procedure. Standard approach did not work. Only the use of nifedipine and verapamil improved patient's resistant hypoglycemia. The proposed rationale is that CCBs reduce or delay insulin secretion by pancreatic beta cells.

Although more clinical studies are needed, it is essential to be aware of the potential benefits of CCBs. For some patients with refractory and devastating hypoglycemia, they could be the last resort. Additionally, physicians are already familiar with CCBs as they have been on the market for decades.

GT

Oral "ozempic" lowers A1c and body weight in patients with type 2 diabetes

Oral "ozempic" lowers A1c and body weight in patients with type 2 diabetes

PIONEER 1 was a 26-week randomized clinical trial conducted in nine countries. It tested the efficacy and safety of oral semaglutide vs. placebo in diabetes patients with baseline A1c 8.0%. A group of 703 adults was monitored and analyzed.

At 24 weeks, the higher dose 14 mg of oral semaglutide reduced A1c and body weight by about 1.2% and 5 lbs respectively. Results were statistically significant. Gastrointestinal side effects were more common with semaglutide than placebo but similar to other GLP-1 agonists in the market.

The above results are promising for oral semaglutide to receive FDA approval.

GT

Landmark NIH study: ultra-processed diet increases body weight

Landmark NIH study: ultra-processed diet increases body weight

Common sense and knowledge tell us that whole food is healthier than processed food. It is nice to now have a rigorous randomized clinical trial proving this concept.

The NIH study shows that even when food calories, energy density, macronutrients, sugar, sodium, and fiber were matched, individuals consuming ultra-processed food gained weight compared to those on unprocessed meals.

This is a landmark study as it can influence guidelines/advice at the national level.

GT

New FDA Approval: hydrogel capsule for weight loss

New FDA Approval: hydrogel capsule for weight loss

About 450 overweight or obese adults with BMI 27-40 kg/m2 were randomized to receive Gelesis100 or placebo. Subjects were followed for 6 months. At the end of the trial, patients receiving Gelesis100 lost a significant amount of weight compared to placebo group: about 60% and 25% of the adults lost ≥5% (≥10 lbs) and ≥10% (≥20 lbs) body weight.

Gelesis100 comes in a capsule form. It is taken with plenty of water twice daily before meals. The capsule contains particles, that in the presence of water, have the capability of expanding massively in the stomach, thus triggering a sense of fullness and decreased appetite.

The particles are not absorbed in the bloodstream. No serious adverse events were seen. Gastrointestinal upset was the most common side effect.

GT

More evidence of Metformin benefits in early prediabetes

More evidence of Metformin benefits in early prediabetes

More good news for metformin. MET-REMODEL trial tested patients with known cardiovascular disease and insulin resistance, but without gross diabetes. Patients received metformin or placebo for 12 months.

Compared to the placebo group, subjects receiving metformin experienced the following improvements in 12 months: Less left ventricular mass index,  less LVM, lower systolic BP, decreased body weight and less oxidative stress.

Early start of metformin could be useful in adults with insulin resistance.  Long term side effects of metformin, however, need to be discussed thoroughly with patients.

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

Addition of Ozempic to a SGLT2 inhibitor improves hyperglycemia and bodyweight

Addition of Ozempic to a SGLT2 inhibitor improves hyperglycemia and bodyweight

Clinical experience has consistently shown that addition of a GLP-1 agonist to a SGLT2 inhibitor improves hyperglycemia in patients with uncontrolled diabetes. Current study SUSTAIN 9 proves just that for semaglutide, a once weekly injectable GLP-1 agonist.

Addition of semaglutide reduced A1c by 1.4% and bodyweight by 8.4 lbs. Results were statistically significant. As expected, the GI side effects were more pronounced with semaglutide. About 72% of patients were also taking metformin and 13% sulfonylurea.

A group of 300 participants were followed for 30 weeks.

GT

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

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

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.

GT

BMI vs. CVD contradiction

BMI vs. CVD contradiction

The study observes that higher BMI is associated with higher cardiovascular mortality and morbidity. On the contrary, it is intriguing to see that CVD longevity is prolonged in adults with elevated BMI (>25) compare to those with normal BMI (19-25). A speculative explanation could be that once cardiovascular illness has been established, the high BMI-induced damage is irreversible and subsequently somewhat protective. Future research will clarify the molecular mechanisms of these observations.

GT

Diabetes and obesity increase the risk of 12 malignancies

Diabetes and obesity increase the risk of 12 malignancies

The article provides more evidence that diabetes and obesity increase the risk of malignancy, particularly of colorectal, gallbladder, pancreas, kidney, liver, endometrial, postmenopausal breast, ovarian, gastric cardia, thyroid cancer, esophageal adenocarcinoma and multiple myeloma. It is estimated that 430 million adults have diabetes worldwide, while 2.0 billions are overweight or obese. How could this global health problem be meaningfully approached?

GT

Bariatric surgery improves mortality outcomes

Bariatric surgery improves mortality outcomes

Bariatric surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve gastrectomy, compared with usual care nonsurgical obesity management, was associated with lower all-cause mortality over a 4.5 years follow-up.

JAMA

Obesity and kidney disease

Obesity and kidney disease

This is a nice review showing how obesity contributes to kidney disease, particularly in the setting of metabolic syndrome, diabetes and hypertension.

The process starts with glomerular hyperfiltration, and made worse by high sodium and animal protein intake. I suspect that inflammation from visceral adiposity plays a major role too.

It appears that the risk for kidney disease accumulates over time, as prognosis is worse in childhood-onset vs. adult-onset obesity.

GT

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

Joint statement on metabolic surgery for diabetes

Joint statement on metabolic surgery for diabetes

Below are listed recommendations on when to consider metabolic surgery for type 2 diabetes. Decisions making would depend on BMI severity and glycemic control.

The joint statement advises surgery for patients with class III obesity, and in those with class II but have high A1c. Consideration should be given to adults with controlled class II or uncontrolled class I obesity. 

Standards are listed below with a slightly modified wording for easier and succinct reading:

GT

2017 ADA guidelines: metabolic surgery for type 2 diabetes

2017 ADA guidelines: metabolic surgery for type 2 diabetes

Obesity is a pro-inflammatory state contributing to insulin resistance and type 2 diabetes. Starting with jejuno-ileal bypass in 1954 by Kremer and intestinal bypass in 1967 by Mason, various techniques of the malabsorption surgery have been developed, researched and applied over the decades. They have shown good results in reducing hyperglycemia, the number of diabetic medications and excessive body weight.

Guidance on the importance and indications of metabolic surgery for type 2 diabetes were published in Diabetes Care, January 2017. Recommendations are listed below with a slightly modified wording for easier and succinct reading:

GT

Healthy obesity, still at risk for ischemic heart disease

Healthy obesity, still at risk for ischemic heart disease

About 6,000 individuals were followed for 10 years. Metabolically healthy obesity was defined by high BMI, but in the absence of HDL, triglyceride, blood pressure and glucose anomalies. Yet authors found that "healthy" obese adults, particularly men, were more likely to develop ischemic heart disease (IHD) then those with normal body weight. The IHD risk was highly elevated, by 3-fold in 10 years.  These findings give us still another reason to avoid high BMI.

GT

Global obesity study: dismal projections

Global obesity study: dismal projections

A global observational study on obesity and its related complications: about 70 million persons from 195 countries were analyzed. Study time span 1980-2015. Obesity and disease burden are on the rise, particularly among children. Cardiovascular disease is the number one killer among those with high BMI. Obesity can cause diabetes, NASH, CVD, kidney disease, musculoskeletal anomalies and various types of malignancies, primarily of GI and GU nature.

How to fix it??

GT

Medications that Promote Weight Loss in Type 2 Diabetes

Medications that Promote Weight Loss in Type 2 Diabetes

Type 2 diabetes is prevalent and a common cause of other conditions such as kidney failure (nephropathy), nerve damage (neuropathy), eye disease (retinopathy), bone infection (osteomyelitis) and heart illness (coronary artery disease). It is primarily due to excessive body weight. So it is natural to look for medications that can help not only with glucose control but also targeting the root problem, obesity.

In the diabetes world, there are two such drug classes, ‘GLP-1 agonists’ and ‘SGLT-2 inhibitors’. Both can assist patients in losing significant body weight. These medications could be expensive, but if covered by health insurance, would be viable options for type 2 diabetes. Of course, side effects and contraindications need to be discussed with the physician.

GT