Obesity and type 2 diabetes mellitus

Obesity as a causative factor for type 2 diabetes

A large prospective longitudinal study has shown that weight gain is associated with an increased risk of type II diabetes mellitus (1).

The study followed 114,281 female nurses in the USA.

A weight increase of 5-7.9 kg during the study was associated with an approximately two-fold increase in risk for type II diabetes. A weight increase of 8-10.9 kg resulted in a three-fold increase in risk.

With respect to the UK (2):

• likelihood and severity of type 2 diabetes are closely linked with body mass index (BMI)
  • a seven times greater risk of diabetes in obese people compared to those of healthy weight, with a threefold increase in risk for overweight people
  • currently 90% of adults with type 2 diabetes are overweight or obese
  • people from black, Asian and other minority ethnic groups are at an equivalent risk of type 2 diabetes at lower BMI levels than white European populations
  • 62% of adults were overweight or obese in England in 2012
  • 6% of people aged 17 years or older had diagnosed diabetes in England in 2013

Surgical treatment of obesity in patients with diabetes

• bariatric surgery has been shown to induce the remission of diabetes or to reduce the need for medications with durable long-term results in morbidly obese patients (3,4,5,6).

Evidence of effectiveness of bariatric surgery in the treatment of type 2 diabetes mellitus (T2DM)

• a meta-analysis compared with non-surgical treatment of obesity, bariatric surgery leads to greater body weight loss and higher remission rates of type 2 diabetes and metabolic syndrome
  • included 11 studies with 796 individuals (range of mean body mass index at baseline 30-52)
    • individuals allocated to bariatric surgery lost more body weight (mean difference -26 kg (95% confidence interval -31 to -21)) compared with non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 22.1 (3.2 to 154.3) in a complete case analysis; 5.3 (1.8 to 15.8) in a conservative analysis assuming diabetes remission in all non-surgically treated individuals with missing data) and metabolic syndrome (relative risk 2.4 (1.6 to 3.6) in complete case analysis; 1.5 (0.9 to 2.3) in conservative analysis), greater improvements in quality of life and reductions in medicine use (no pooled data)
    • plasma triglyceride concentrations decreased more (mean difference -0.7 mmol/L (-1.0 to -0.4) and high density lipoprotein cholesterol concentrations increased more (mean difference 0.21 mmol/L (0.1 to 0.3))
    • changes in blood pressure and total or low density lipoprotein cholesterol concentrations were not significantly different
    • there were no cardiovascular events or deaths reported after bariatric surgery
      • most common adverse events after bariatric surgery were iron deficiency anaemia (15% of individuals undergoing malabsorptive bariatric surgery) and reoperations (8%)
        
        
• a cohort of 217 patients with T2DM who underwent bariatric surgery between 2004 and 2007 and had at least 5-year follow-up were assessed. Complete remission was defined as glycated hemoglobin (A1C) less than 6% and fasting blood glucose (FBG) less than 100 mg/dL off diabetic medications (4)
  • demonstrated that 24% of all patients and 31% of gastric bypass patients achieved long-term complete remission with an A1C less than 6.0% and that 27% of the gastric bypass patients sustained that level of glycemic control off medication continuously for more than 5 years
  • as seen in other studies this study demonstrated that (Roux en Y gastric bypass) RYGB had a higher long-term rate of diabetes remission than restrictive procedures
    
    
• a 3 year follow-up of cohort of 256 of 316 randomised patients found metabolic/bariatric surgery is more effective than medical/lifestyle intervention in remission of type 2 diabetes (HbA1c <=6.5% for 3 months without usual glucose-lowering therapy in 37.5% vs. 2.6%, p<0.001)(5)

Principles of metabolic surgery:

• the finding that glucose homeostasis can be achieved with a weight loss-independent mechanism immediately after bariatric surgery (6,7), especially gastric bypass, has led to the paradigm of metabolic surgery
  
  
• mechanisms of metabolic gastrointestinal surgery are thought to depend on the dramatic entero-hormonal changes after physio-anatomical re-arrangement of the gastrointestinal tract. However, data have shown that weight loss is still the cornerstone of diabetes remission
  
  
• considering weight loss-independent mechanisms for diabetes improvement, metabolic gastrointestinal surgery is now being performed for mildly obese or even overweight patients (BMI < 35 kg/m2), with a focus on diabetes rather than obesity (7)

NICE state (8):

• for recent onset type 2 diabetics
  • offer an expedited assessment for bariatric surgery to people with a BMI of 35 or over who have recent-onset type 2 diabetes as long as they are also receiving or will receive assessment in a tier 3 service (or equivalent
    
    
  • consider an assessment for bariatric surgery for people with a BMI of 30-34.9 who have recent-onset type 2 diabetes as long as they are also receiving or will receive assessment in a tier 3 service (or equivalent)
    
    
  • consider an assessment for bariatric surgery for people of Asian family origin who have recent-onset type 2 diabetes at a lower BMI than other populations as long as they are also receiving or will receive assessment in a tier 3 service (or equivalent)
    
    
• bariatric surgery is a treatment option for people with obesity per se if all of the following criteria are fulfilled:
  • they have a BMI of 40 kg/m2 or more, or between 35 kg/m2 and 40 kg/m2 and other significant disease (for example, type 2 diabetes or high blood pressure) that could be improved if they lost weight
    • all appropriate non-surgical measures have been tried but the person has not achieved or maintained adequate, clinically beneficial weight loss
    • the person has been receiving or will receive intensive management in a tier 3 service
    • the person is generally fit for anaesthesia and surgery
    • the person commits to the need for long-term follow-up

Reference:

1. Colditz, GA, Willett, WC, et al. (1995). Weight gain as a risk factor for clinical diabetes mellitus in women. Ann. Intern. Med. 122: 481-6
2. PHE (2014).Adult obesity and type 2 diabetes
3. Gloy VL, Briel M, Bhatt DL, Kashyap SR, Schauer PR, Mingrone G, et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ 2013;347:934
4. Brethauer SA et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg. 2013 Oct;258(4):628-36; discussion 636-7.
5. Kirwan JP et al. Diabetes Remission in the Alliance of Randomized Trials of Medicine Versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D). Diabetes Care 2022; dc212441. https://doi.org/10.2337/dc21-2441
6. Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic conditions in adults.BMJ. 2014 Aug 27;349
7. Pok EH, Lee WJP.Gastrointestinal metabolic surgery for the treatment of type 2 diabetes mellitus. World J Gastroenterol. 2014 Oct 21;20(39):14315-14328.
8. NICE (November 2014).Obesity: identification, assessment and management of overweight and obesity in children, young people and adults