Effects of Polymorphism rs3123554 in the Cannabinoid Receptor Gene Type 2 (Cnr2) on Body Weight and Insulin Resistance after Weight Loss with a Hypocaloric Mediterranean Diet

The epidemic of both obesity and type 2 diabetes is due to environmental factors, but the individuals developing the conditions possess a strong genetic predisposition. Observational surveys and intervention studies have shown that excess body fatness is the major environmental cause of type 2 diabetes, and that even a minor weight loss can prevent its development in high-risk subjects. Maintenance of a healthy body weight in susceptible individuals requires 45–60 minutes physical activity daily, a fat-reduced diet with plenty of fruit, vegetables, whole grain, and lean meat and dairy products, and moderate consumption of calorie containing beverages. The use of table values to predict the glycemic index of meals is of little – if any – value, and the role of a low-glycemic index diet for body weight control is controversial. The replacement of starchy carbohydrates with protein from lean meat and lean dairy products enhances satiety, and facilitate weight control. It is possible that dairy calcium also promotes weight loss, although the mechanism of action remains unclear. A weight loss of 5–10% can be induced in almost all obese patients providing treatment is offered by a professional team consisting of a physician and dieticians or nurses trained to focus on weight loss and maintenance. Whereas increasing daily physical activity and regular exercise does not significantly effect the rate of weight loss in the induction phase, it plays an important role in the weight maintenance phase due to an impact on daily energy expenditure and also to a direct enhancement of insulin sensitivity.

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Comparison of Sleeve Gastrectomy and Conservatory Treatment Effect on Biochemical and Hormonal Profile of Obese Type 2 Diabetes Subjects: CREDOR Randomized Controlled Study Results

Revista de Chimie ◽

10.37358/rc.17.7.5730 ◽

2017 ◽

Vol 68 (7) ◽

pp. 1622-1627 ◽

Cited By ~ 1

Author(s):

Diana Simona Stefan ◽

Andrada Mihai ◽

Daiana Bajko ◽

Daniela Lixandru ◽

Laura Petcu ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Sleeve Gastrectomy ◽

Beta Cell ◽

Beta Cell Dysfunction ◽

Control Group ◽

Cell Dysfunction ◽

Randomized Controlled

Metabolic surgery is the most efficacious method for the treatment of morbid obesity and was recently included among the antidiabetes treatments recommended in obese type 2 diabetes (T2D) patients. The aim of this study was to compare in a randomized controlled trial the effect of sleeve gastrectomy (SG) to that of intensive lifestyle intervention plus pharmacologic treatment on some markers of insulin resistance and beta cell function as well as some appetite controlling hormones in a group of male obese T2D subjects. The study groups comprised 20 subjects for SG and 21 control subjects. Fasting blood glucose, insulin, proinsulin, adiponectin, leptin, ghrelin, HOMA-IR, HOMA-%B, proinsulin-to-insulin ratio and proinsulin-to-adiponectin ratio were evaluated at baseline and after one year follow-up. Overall, patients in the SG group lost 78.98% of excess weight loss (%EWL) in comparison with 9.45% in the control group. This was accompanied by a significant improvement of insulin resistance markers, including increase of adiponectin and decrease of HOMA-IR, while no changes were recorded in the control group. Weight loss was also associated with a significant improvement of proinsulin-to-insulin and proinsulin-to-adiponectin ratio, both surrogate markers of beta cell dysfunction. These also improved in the control group, but were only marginally significant. Our findings suggest that improved insulin resistance and decreased beta cell dysfunction after sleeve gastrectomy might explain diabetes remission associated with metabolic surgery.

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Association of insulin resistance and leptin receptor gene polymorphism in type 2 diabetes mellitus

Journal of the Chinese Medical Association ◽

10.1097/jcma.0000000000000507 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Usha Adiga ◽

Nandit Banawalikar ◽

Sriprajna Mayur ◽

Radhika Bansal ◽

Nafeesath Ameera ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphism ◽

Leptin Receptor ◽

Receptor Gene ◽

Receptor Gene Polymorphism

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Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults with Overweight or Obesity and Type 2 Diabetes Mellitus: A 54-Week Randomized Phase 2b Study

10.2337/figshare.14272955.v1 ◽

2021 ◽

Author(s):

Rajaa Nahra ◽

Tao Wang ◽

Kishore M. Gadde ◽

Jan Oscarsson ◽

Michael Stumvoll ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Body Weight ◽

Ad Hoc ◽

Open Label ◽

Double Blind ◽

Glucagon Receptor ◽

Nonalcoholic Fatty Liver ◽

Design And Methods

<a>Objective: </a>Cotadutide, a <a>dual GLP-1 and glucagon receptor agonist</a>, is under development for nonalcoholic steatohepatitis (NASH) and type 2 diabetes. The effects of cotadutide on hepatic and metabolic parameters were evaluated in participants with overweight/obesity and type 2 diabetes. Research Design and Methods: In this phase 2b study, 834 adults with BMI ≥25kg/m2 and type 2 diabetes inadequately controlled with metformin (glycated hemoglobin A1c [HbA1c] of 7.0%─10.5% [53─91 mmol/mol]) were randomized to double-blind cotadutide 100µg (n=100), 200µg (n=256), or 300µg (n=256), placebo (n=110), or open-label liraglutide 1.8mg (n=110), all administered subcutaneously (NCT03235050). Coprimary endpoints were changes in HbA1c and body weight at week 14. The originally randomized interventions were continued to week 54. Liver damage biomarkers and liver fibrosis algorithms were assessed. Results: Cotadutide significantly decreased HbA1c and body weight at weeks 14 and 54 versus placebo (all P<0.001). Improvements in lipid profile, aspartate aminotransferase and alanine aminotransferase levels, <a>PRO-C3 level, fibrosis-4 index</a>, and <a>nonalcoholic fatty liver disease fibrosis score</a> were observed with cotadutide 300µg versus placebo, but not with liraglutide. Weight loss with cotadutide 200µg was similar to liraglutide 1.8mg, and greater with cotadutide 300µg versus liraglutide 1.8mg. <a>The most common adverse events with cotadutide (nausea, 35%; vomiting, 17%) decreased over time. </a> Conclusions: Cotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH.

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