Diabetes, Weight loss | March 1, 2016 | Author: The Super Pharmacist
Most patients with type 2 diabetes are overweight or obese, and the global epidemic of obesity is commonly thought to explain the dramatic increase in the prevalence of type 2 diabetes mellitus (T2DM) over the past 20 years. Both overweight and obesity are major risk factors for heart disease, type 2 diabetes mellitus (T2DM), hypertension, stroke and certain cancers (bowel, oesophageal and pancreatic cancer). Over the past three decades, the number of people with diabetes mellitus has more than doubled globally. The global epidemic of T2DM is tied to rising rates of overweight and obesity in adults as well as in youth.
Overweight or obesity are the single most important predictors of T2DM, and the effect of obesity on lifetime risk of T2DM is stronger in younger adults. Type 2 diabetes, formerly called adult-onset diabetes, is the most common type of diabetes. About 90 to 95 percent of people with diabetes have type 2. While it usually affects older adults, younger people, even children, are getting T2DM. Type 2 diabetes among Australian Caucasians appears to show prevalence rates which are comparable to those reported for Caucasians elsewhere, with an age-standardised prevalence of approximately 5% to 6%. However, much higher prevalence rates are seen in non-Caucasian ethnic groups. Age-adjusted prevalence rates in urban Aborigines now exceed 20% and approach 25% in Aborigines with a long history of acculturation.
Elevated concentrations of glucose (sugar) in the blood (e.g. after a meal) stimulate the release of the hormone, insulin, from the β-cells in the pancreas gland. Insulin regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from nutrients in the intestinal tract and then facilitating the uptake, utilization, and storage of glucose by the cells of the body.
Obesity contributes to insulin resistance. Insulin resistance is a physiological condition where the body produces insulin, but the cells in the body become resistant to insulin and are unable to use it as effectively, leading to hyperglycemia (high blood sugar).
Obesity is also associated with impairment of pancreatic β-cell function which leads to a reduction in insulin production and high blood sugar levels.
The evidence that bariatric surgery improves the control of blood sugar levels in severely obese patients with type 2 diabetes was first recognised almost 2 decades ago.
There are four types of bariatric operations that are commonly offered in the United States:
Diabetes resolution after roux-en-Y gastric bypass surgery (RYGB) surgery was formerly attributed to the effects of weight loss after surgery. However, this did not explain why diabetes resolution occurred within several days while weight loss would require several months. It was subsequently recognised that these operations must offer direct metabolic effects independent of weight loss, and these procedures were renamed as 'metabolic operations.’
The direct metabolic effects of gastric bypass surgery are believed to include biochemical enhancement of fat metabolism, changes in gut hormonal and nerve signals, and pronounced shifts in gut bacterial flora. A combination of these effects could explain the rapid normalisation of blood sugar control in patients following RYGB surgery.
Evidence from recent animal studies and humans suggests that the rapid return to euglycemia (normal blood sugar levels) seen in T2DM patients after RYGB may be attributed to exclusion of the duodenum from the flow of nutrients. The largest meta-analysis of bariatric surgery demonstrating resolution of T2DM included 621 studies and 135,246 patients. Overall, 78.1% of diabetic patients in the analysis showed complete resolution of type 2 diabetes and an additional 8.5% of patients showed an improvement in their condition. Weight loss and type 2 diabetes resolution were greatest for patients undergoing duodenal switch, followed by gastric bypass, and least for gastric banding procedures. These results indicate that the greater the weight loss with surgery the higher the resolution rate in T2DM. In a recent retrospective case-matched study of 86 morbidly obese patients with type 2 diabetes who had undergone medical management were compared with matched type 2 diabetes patients who had undergone either RYGB or adjustable gastric banding (AGB) or biliopancreatic diversion with duodenal switch (BPD-DS). The patients who underwent RYGB had greater weight loss, HbA1c normalisation, and medication score reduction compared to both non-surgical control-matched patients and AGB-matched patients. Hemoglobin A1c is an important blood test that reflects how well diabetes is being controlled in a given patient over the past 2 to 3 months. Results showed resolution of diabetes at 1 year in 20%, 60% and 81.5% of AGB, RYGB patients and duodenal switch patients, respectively. The patients who underwent duodenal switch had greater reductions in HbA1c, but weight loss was similar to RYGB patients. These results also confirm that surgical procedures inducing greater weight loss are associated with higher type 2 diabetes resolution rates. In another randomised trial, 150 obese patients with uncontrolled type 2 diabetes received intensive medical therapy alone or medical therapy plus laparoscopic RYGB or laparoscopic sleeve gastrectomy (LSG). The researchers concluded that in patients with uncontrolled T2DM, 12 months of medical therapy plus bariatric surgery achieved glycaemic control in significantly more patients than medical therapy alone. In another prospective randomised trial, 60 patients were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion (BPD).17 Diabetes remission at 2 years failed to occur in the medical therapy group, but remission was observed in 75% of the RYGB group and 95% of the BPD group.
Growing evidence indicates that certain operations involving intestinal diversions improve glucose homeostasis through varied mechanisms beyond reduced food intake and body weight. Possible mechanisms include alteration of gut hormones.
An endoscopic procedure that alters the inner surface of the duodenum and produces sustained HbA1c improvements for patients with T2DM was introduced this year by Dr. Francesco Rubino of NewYork-Presbyterian Hospital/Weill Cornell Medical Center at the 19th World Congress of International Federation for the Surgery of Obesity & Metabolic Disorders. Developed by Fractyl Labs, the noninvasive Revita Duodenal Mucosal Resurfacing (DMR) procedure involves the use of thermal ablation with a hot water balloon to resurface a portion of the mucus cells lining the duodenum. Under endoscopic management, surgeons performed thermal ablation of the duodenal mucosa with the Revita System on 30 patients with uncontrolled diabetes and HbA1c levels averaging 9.2 prior to treatment. In the 19 patients who received DMR over several centimeters of their duodenum, HbA1c levels dropped to 7.1, on average, after three months and remained stable six months after the procedure. The treatment effect appears to be dose-dependent, as those patients who received DMR over a shorter segment of their duodenum did not experience as significant of a benefit. The gastrointestinal tract appears to play a critical role in the regulation of glucose metabolism, but the exact nature of upper intestinal dysfunction in T2DM is still unclear. Dr. Rubino proposes the "anti-incretin theory."19 Incretins are gastrointestinal hormones, produced in response to the transit of nutrients, boost insulin production. Because an excess of insulin can cause hypoglycemia (extremely low levels of blood sugar) — a life-threatening condition — Dr. Rubino speculates that the body has a counter-regulatory mechanism (or "anti-incretin" mechanism), activated by the same passage of nutrients through the upper intestine. The latter mechanism would act to decrease both the secretion and the action of insulin. He postulates that, in healthy patients, a correct balance between incretin and anti-incretin factors maintains normal excursions of sugar levels in the bloodstream. In diabetics, however, the duodenum and jejunum may be producing too much of this anti-incretin, thereby reducing insulin secretion and blocking the action of insulin, ultimately resulting in Type 2 diabetes. After gastrointestinal bypass procedures, the exclusion of the upper small intestine from the transit of nutrients may offset the abnormal production of anti-incretin, thereby resulting in remission of diabetes.
The terms "metabolic" and "diabetes surgery" indicate a surgical approach whose primary intent is the control of metabolic alterations and hyperglycemia in contrast to "bariatric surgery," conceived as a mere weight-reduction therapy. Despite significant effort and numerous drug options, nearly half of the diabetic population in the U.S. and Europe will become poorly controlled. In 2012, complications associated with high blood sugar levels in patients with type 2 diabetes cost the U.S. healthcare system $245 billion, a 41% increase over the prior five-year period. These costs are expected to rise dramatically as the population ages and more people develop the disease. Many studies have looked at the cost-effectiveness of bariatric surgery and concluded that the costs of surgery are recouped within 2–5 years of the operation.20-22 Today, most patients with diabetes are not offered a surgical option, and bariatric surgery is recommended only for those with severe obesity (BMI > 35kg). The Revita DMR procedure promises improvement or even remission of the disease for those diabetics with lower BMI scores. The Revita DMR procedure could be a compelling option for millions of patients, particularly those who are failing oral therapy and are transitioning to complicated drug regimens that may include insulin.
Quoted mortality rates for bariatric surgery range from 0.1% to 1% for LAGB and RYGB respectively. In high risk patients this may be higher, and it is essential that decision making is coordinated by an experienced multidisciplinary team. A gastric bypass specific and validated mortality risk scoring system exists to assist clinicians in risk assessment and stratification. More clinical trials in this field are a priority in order to better understand how diabetic surgery compares to other treatment options and when the benefits of surgery outweigh its risks. Clinical guidelines for diabetes surgery will certainly be different from those for bariatric surgery, and should not be based only on BMI levels.
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