Type 2 diabetes mellitus

 

This blog provides free general information for anyone who is seeking to understand more about obesity and type 2 diabetes, not intended as a medical consult. Please seek proper medical advice for individual assessment and management.

The crucial learning points are:

  • What is Type 2 diabetes mellitus
  • The difference between pharmacological (medications) and surgical treatment for diabetes
  • What is the extra benefits of bariatric/metabolic surgery

Please refer to the section on “Understanding visceral obesity and metabolic syndrome” for further information on metabolic syndrome.

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Epidemic of obesity and Type 2 diabetes (T2DM)

If there is such a thing as “modern disease of affluence” in the society that we live in, where there is abundance of easily available food, technology to improve our lives and sedentary activities as our main forms of entertainment, then it is not surprising that we are seeing a massive rise in the rates of obesity, T2DM, metabolic syndrome and cardio-vascular disease in Western societies.

20% of obese patients have diabetes and the prevalence of metabolic syndrome in diabetics is 80%. T2DM is estimated to cause up to 50% of end stage kidney disease and 60% of coronary artery disease, as well as a range of microvascular complications such as retinopathy and peripheral neuropathy.

In the early part of the 21st century there is already a global pandemic of obesity and T2DM in many OECD countries and extending to many rapidly developing nations as well. Current strategies (lifestyle modifications and pharmacological therapies) for prevention of obesity and T2DM are failing. Health authorities are struggling to develop strategies to treat obesity/T2DM or prevent its complications and are turning to bariatric/metabolic surgery as the mainstay of treatment, for now at least until more effective medical therapy becomes available in the future.

So far bariatric/metabolic surgery is the only proven effective strategy not only to reduce excess weight, reduce medical co-morbidities associated with obesity but also proven to reduce obesity/diabetes related cardiovascular morbidity and mortality. Surgery is now adopted into the treatment algorithms by Diabetes organizations around the world, especially for patients with BMI>35.

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Type 2 diabetes mellitus

T2DM is essentially insulin resistance in the liver and/or periphery tissues (mainly skeletal muscles). Instead of normal deposition of triglycerides into adipocyte fat cells, there is triglyceride deposition in the liver, skeletal muscle and endothelial cells, termed “ectopic fat”. The ectopic triglyceride contributes to tissue lipotoxicity, which is very damaging to insulin signalling pathways, blocks intra cellular action of insulin and results in insulin resistance.

The insulin resistance state is also often associated with metabolic syndrome, endothelial dysfunction, pro-coagulant and a perpetual chronic inflammatory state. The free fatty acids and damaging toxic chemical substances generate continuous stimulus for Beta cell destruction and the progression of diabetes. T2DM is now regarded as a chronic metabolic disease with continuous decline in pancreas beta cell function.

Oral medication only treats the symptoms by reducing the high blood sugar levels but does not treat the underlying disease and is not a permanent solution. Optimal control of blood sugar can’t be achieved or sustained with medical therapy alone with less than half of patients achieve HbA1C levels of <7% and often there is escalation of treatment with time, where multiple medications in increasing doses are required or eventually the introduction of insulin for those with end stage disease.

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The proper treatment for T2DM

As mentioned above, oral medications is only to reduce the blood glucose back to relative normal levels and treat the symptoms of hyperglycaemia. Even with additions of newer forms of medications (such as GLP-1 analogues and DPP4 inhibitors) control of diabetes have been proven to be suboptimal.

It is estimated that 50-92% of type 2 diabetics are obese and the use of oral medications +/- insulin is associated with further weight gain.

Hence treatment for amelioration of T2DM ideally involves:

*Increase insulin release from the pancreas or reduce tissue insulin resistance

  • Weight loss have been proven to improve insulin sensitivity in obese individuals
  • Metabolic operations such as the sleeve gastrectomy and gastric bypass has incretin hormone effect (the hindgut theory)
  • Return of blood sugar down to acceptable levels, to allow patients to reduce the doses of medications or to be able to come off the medications completely

*Reduction of fatty liver disease and the ectopic fat in liver tissues

  • Weight loss reduces liver steato-hepatitis and reduces central/visceral fat, which in turns improves glucose sensitivity in the liver and halts gluconeogenesis

Bariatric/metabolic surgery is proposed to provide a cure (or at least a temporal cure for T2DM and halt the progression of the chronic disease) and addresses multiple factors at the same time by:

  • Reduction of excess weight, central/visceral fat stores
  • Reduction in the chronic inflammatory states
  • Reduction in the insulin resistant and metabolic state
  • Reduction in cardio-vascular complications and endothelial damage associated with obesity and diabetes

The above cannot be achieved by medical or pharmacological therapies alone at this stage. With the realization that morbid obesity, T2DM and metabolic syndrome are potentially inter-related and that the many individual components (metabolic, oxidative, chronic inflammatory states) that need to be addressed altogether, this has led to a paradigm shift and major changes in management protocol amongst physicians and surgeons.

Metabolic surgery for type 2 diabetes mellitus

There is a growing interest in bariatric surgery to treat diabetes associated with obesity (BMI>35 for the Caucasian population standard). Laparoscopic bariatric/metabolic surgery is now included into treatment algorithms for T2DM because studies comparing surgery versus non operative management, have conclusively proven superior results in the surgical group in terms of better HbA1C results and lower fasting glucose levels. There is better overall amelioration of obesity and diabetes, with optimal glycaemic control and minimal oral diabetic medication use in the surgical group.

In the past the remission rate for T2DM after bariatric/metabolic surgery has been reported in up to 95% of cases. The excellent result is achieved because different definitions may have been used to describe as resolution for hyperglycaemia. Recently more standard/universal definitions have emerged.

In 2009 the American Diabetes Association (ADA) described resolution of T2DM as either partial or complete after 1 year without pharmacological treatment.

*Partial resolution:

  • HbA1C <6.5%, fasting blood glucose 100-125mg/dL (5.6-6.9 mmol/L)

*Complete resolution:

  • HbA1C <5.6%, fasting blood glucose <100mg/dL (<5.6 mmol/L)

At present most studies consistently report over 50% T2DM resolution after surgery. Not all patients achieved complete resolution according to the standard above or achieved total cessation of medications. The chances of diabetes remission improve with shorter duration of diabetes (<5 years), absence of insulin treatment (before Beta cell exhaustion or failure) and the extent of weight loss after surgery. Nevertheless there are immeasurable benefits to improvements in metabolic control, reduction of the oxidative stress and chronic inflammation (associated with morbid obesity) and many patients are able to reduce the doses of diabetic medications.

Hormonal influences from metabolic surgery

After Roux Y gastric bypass and sleeve gastrectomy, clinical improvement in glycaemic control has been reported early (within 1 week) in the post-operative period before any significant excess weight loss has been achieved. The mechanism or the scientific reason for this is yet to be confirmed but it is believe that the hindgut theory plays an important part.

After bariatric/metabolic surgery, rapid delivery of food or nutrients to the distal small bowel results in the early release of hindgut hormones.

  • GLP-1 has a direct incretin effect on pancreatic Beta cells to stimulate release of insulin. GLP-1 also induces satiety and reduces gastric emptying to stop the over eating and facilitates weight loss.
  • GIP may also acts directly on pancreatic cells to improve insulin sensitivity.
  • PYY is co-secreted with GLP-1, increases satiety and stop over eating, acting as the ileal brake phenomenon.

It is believed that the early improvement in diabetes (after Roux Y gastric bypass and sleeve gastrectomy) is associated with improvements in central insulin sensitivity and reduced liver lipotoxicity. The exact mechanisms are not clear but it is believed that hindgut hormones (described above) and ghrelin hormones play a major part in the process. The peripheral tissue (skeletal muscle) does not contribute to early metabolic improvement or increased peripheral insulin sensitivity but rather this occurs later, after significant weight loss and peripheral subcutaneous fat loss.

The reduction in the orexigenic Ghrelin hormone after bariatric surgery is believed to have a significant effect in reducing hunger (appetite stimulation), consequently resulting in weight loss and associated recovery from T2DM. However improvements in blood glucose control has been observed early in the post-op period before significant weight loss has been achieved. This is thought to be due to the fact that ghrelin normally function to inhibit pancreatic insulin secretion and stimulate the release of counter regulatory hormones (to increase blood glucose). Thus the reduction of ghrelin after gastric resection or diversion is believed to be an important step facilitating a return to normal glycaemic control.

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T2DM relapse rates

Unfortunately T2DM is a progressive disease and with inevitable weight re-gain after bariatric surgery, there is also a risk for relapse of T2DM despite initial success or complete resolution.

The success of metabolic surgery or remission rate of T2DM is better amongst patient with shorter duration of the disease (<5 years) and in those who achieved more weight loss at 2 years. This indicates that surgery should be performed early in the disease stage before significant Beta cell destruction has occurred, while there is still a chance for the pancreas to recover and have enough physiological reserve to continue insulin production.

Similarly the relapse rate is higher amongst those with longer duration of the disease, has been on intense medical therapy (big doses or combination of oral hypoglycaemic medications or even insulin), higher blood glucose levels and greater BMI at baseline as well as less weight loss at 2 years after surgery, higher levels of fasting blood glucose and smaller reduction in plasma insulin at 2 years.

At the present time there is minimal disagreement between health experts in recommending obese patients (BMI>35) with T2DM for bariatric/metabolic surgery. But because the evidence for surgery for those with BMI<30-35 is lacking and that the potential for relapse does exist, surgery is not the standard of care for diabetics who are not severely obese, until more research is performed to prove its case.

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Summary

 

Metabolic surgery has been proven to achieve better glycaemic control than intensive medical/pharmacological therapies. Not only that surgery also has the potential to achieve partial or complete resolution of T2DM associated with obesity. At the very least this is an important step in the temporary cessation in the progression of T2DM, now regarded as a chronic disease.

It is important to re-iterate that the reasons for recommending bariatric/metabolic surgery is because it also treats severe/morbid obesity, reduces excess visceral fat, addresses the metabolic syndrome, diminishes cardio-vascular risk factors and reduces morbidity and mortality.

Most health professionals would recommend surgery for those with T2DM and BMI>35. Surgery is more likely to benefit those in the early stage of diabetes and remission is less likely for those with advanced diabetes (bordering on Beta cell exhaustion/failure).

The following statements have been repeated many times by many health professions and found in many journal publications:

  • Bariatric/metabolic surgery has the potential to provide partial or complete remission of T2DM that can’t be achieved with medications alone (at this stage).
  • Surgery (such as sleeve gastrectomy and gastric bypass) promotes release of incretin upon eating without requiring patients to take medications to achieve the same effect.
  • Surgery has been proven to achieve better results (in terms of HbA1C and fasting blood glucose measurements) compare to optimal medical therapy alone.
  • Surgery does not just treat diabetes but address many other issues such as the excess weight, metabolic syndrome and cardiovascular risk factors and has been proven to reduce premature mortality.
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