Diabetes, Obesity and Bariatric Surgery

Diabetes mellitus is a metabolic condition characterized by high levels of blood glucose, or hyperglycemia. Glucose is a form of sugar that serves as an important source of fuel for the body’s cells. It is produced in small quantities by the liver but also enters the blood stream via the gut following digestion of carbohydrate-rich foods. Glucose that is not required for immediate use can be stored within fat, liver and muscle cells as glycogen or fat.

Injecting Insulin

The hormone insulin, produced by beta cells in the pancreas and released in response to an increase in blood glucose after a meal, instructs cells to absorb glucose from the blood stream.

If insufficient insulin is present and/or the body’s cells do not respond to it appropriately, the cells cannot use or store glucose, resulting in glucose intolerance and hyperglycemia.

There are several different forms of the diabetes, including type 1, type 2 and gestational diabetes. The latter two forms are strongly associated with obesity. Symptoms common to type 1 and type 2 diabetes include excessive thirst, frequent urination, extreme fatigue, blurred vision and increased hunger. Onset of type 2 diabetes is typically much more gradual than that of type 1 diabetes, with symptoms taking far longer to manifest.

Type 1 Diabetes

Type 1 diabetes occurs when the pancreatic beta cells stop producing insulin. Also known as juvenile, early-onset or insulin-dependent diabetes, type 1 diabetes is a chronic incurable condition most frequently diagnosed prior to the age of 40, requiring lifelong dependence upon synthetic or animal-derived insulin products in conjunction with dietary modifications to manage glucose levels. Genetic factors are known to play a part in pathogenesis of type 1 diabetes and many cases are thought to occur as a result of autoimmune mediated beta cell damage. Less commonly, type 1 diabetes may occur secondary to chronic pancreatitis; a condition in which the pancreas undergoes scarring and damage as a result of prolonged inflammation. Alcohol misuse is the most common cause of chronic pancreatitis but autoimmune and idiopathic cases are also possible.

Type 2 Diabetes

Type 2 diabetes is by far the most common form of the condition. Sometimes known as acquired, adult-onset or non-insulin-dependent diabetes, it is strongly associated with obesity as well as with a combination of modifiable and non-modifiable risk factors including diet, lack of physical activity, age and family history. It occurs when cells fail to respond appropriately to normal levels of insulin; a state known as insulin resistance, which can occur in parallel with impaired insulin production.

Insulin resistance is a significant complication of obesity and the majority of individuals diagnosed with type 2 diabetes in the US are obese. However, many obese individuals do not develop diabetes, and a common causal pathway has yet to be established. It is clear that fat distribution is significant in the pathogenesis of insulin resistance and type 2 diabetes in obese individuals, with central obesity particularly implicated. Why this should be the case remains unclear, but it has been hypothesized that centrally distributed adipose tissue, known as visceral fat, is more metabolically active than the subcutaneous fat predominantly located in the lower body, although both forms of adipose tissue can have a significant metabolic impact when present in excessive quantities.

Obesity is classed as a chronic inflammatory state, with sustained exposure to superfluous levels of nutrients leading to cell damage within the metabolic tissues of the pancreas, liver, brain, skeletal muscle and other parts of the body via a range of mechanisms. This damage can contribute towards development of insulin resistance as well as beta cell dysfunction, resulting in a vicious cycle in which insulin resistance creates an increased demand for insulin production that cannot be met by the dysfunctional beta cells. However, since not all obese individuals develop type 2 diabetes, additional factors are likely to be involved.

The beta cells of obese individuals with normal blood glucose levels have been found to be larger and to produce more insulin than those of non-obese individuals, making them better equipped to deal with the elevated levels of blood glucose that occur as a result of obesity-induced insulin resistance. These adaptations are believed to occur as a compensatory response to chronic insulin resistance, with failure to mount such a response resulting in progression to overt type 2 diabetes. Several animal studies have reported a link between obesity-related  type 2 diabetes and the protein Pdx1, finding that not only is Pdx1 required in order for beta cells to increase their number and function in response to insulin resistance, but Pdx1 deficiency can lead to beta cell dysfunction and death. It is therefore possible that mutations in the gene responsible for expressing Pdx1 are involved in pathogenesis of obesity-related type 2 diabetes, although such a link has yet to be established in humans.

Type 2 diabetes is a progressive condition, so whilst lifestyle modifications such as dietary changes, weight loss and regular exercise can be sufficient to keep blood glucose levels within safe limits for some time, medical intervention may be required as the condition worsens over time. Most commonly, drugs such as Metformin, which inhibits glucose production by the liver and increases insulin sensitivity, or other medications that slow glucose absorption from the gut or stimulate the pancreatic beta cells to produce more insulin are prescribed. As the pancreas becomes increasingly less efficient at insulin production, use of injectable insulin may eventually become necessary.

Gestational Diabetes

Gestational diabetes mellitus is defined as glucose intolerance with onset or initial diagnosis during pregnancy. Insulin resistance increases during the second and third trimesters of pregnancy in response to increased maternal adiposity and placental production of hormones including human placental lactogen (HPL), cortisol, estrogen and progesterone to ensure the developing fetus receives an adequate supply of glucose and nutrients. In most cases a compensatory increase in insulin production will be triggered. However, some women fail to produce enough insulin to cope with these elevated glucose levels, particularly during the third trimester. Why this should occur only in some individuals remains unclear.

The beta cells of most women who develop Gestational diabetes mellitus have been found to exhibit reduced function as a result of chronic insulin resistance with onset prior to pregnancy.  Obesity is a significant risk factor for developing Gestational diabetes mellitus but the findings with respect to beta cell function have been observed in obese and non-obese women, suggesting that insulin resistance may be a primary mediating factor in obesity-related risk.

Gestational diabetes mellitus is a risk factor for developing overt diabetes, and several long-term studies have indicated that the majority of women who experience Gestational diabetes mellitus will develop type 2 diabetes within ten years of delivery. Additionally, these women are often at increased risk of developing metabolic syndrome. It has yet to be established whether the physiological stresses of pregnancy reveal a pre-existing susceptibility to these conditions, or if some other mechanism is involved.

A small minority of women are thought to develop diabetes during pregnancy as a result of autoimmune destruction of beta cells, as occurs in type 1 diabetes. Development of overt diabetes subsequent to pregnancy is particularly common in such cases and it is possible that these women had previously undiagnosed type 1 diabetes and/or may have gone on to develop diabetes irrespective of pregnancy.

Women with Gestational diabetes mellitus have higher rates of cesarean sections and induced deliveries, and exhibit increased susceptibility to pre-eclampsia. Gestational diabetes mellitus is also linked to excessive fetal growth and increased risk of perinatal complications including macrosomia, shoulder dystocia, neonatal hypoglycemia and hyperbilirubinemia. The offspring of mothers with Gestational diabetes mellitus are also predisposed to glucose intolerance and metabolic syndrome in childhood.

Lifestyle modification is the primary treatment approach for Gestational diabetes mellitus, with dietary changes in conjunction with moderate exercise frequently effective in managing the condition. If blood glucose monitoring indicates that such measures are not providing sufficient control over glucose levels, or where excessive fetal adiposity is detected, insulin therapy may be indicated.

Complications of Diabetes

Diabetes becomes more difficult to manage as the condition progresses and, if left untreated, can lead to a range of chronic and acute complications, particularly in the presence of other health problems such as hypercholesterolemia and hypertension as well as lifestyle factors such as smoking and leading a sedentary lifestyle.

Complications include kidney disease, retinopathy, sexual dysfunction, visual impairment, gum disease, susceptibility to respiratory infections and diabetic neuropathy. Diabetes is a significant risk factor for cardiovascular disease, depression, certain forms of cancer, bone and joint problems including osteoarthritis and osteoporosis, polycystic ovarian syndrome (PCOS), sleep disorders such as obstructive sleep apnea and restless leg syndrome and the skin disorder necrobiosis. There is also a growing body of evidence to suggest that diabetes may be associated with development of Alzheimer’s disease.

Hyperosmolar Hyperglycemic State (HHS) is a particularly dangerous complication of type 2 diabetes that occurs in individuals with very high blood glucose levels. Frequently precipitated by an illness or infection that leads to reduced fluid intake and/or interferes with regular usage of diabetic medications, HHS occurs when severe dehydration triggered by extreme hyperglycemia is not compensated for by increased oral intake of water. HHS usually develops over the course of a few days or weeks and is characterized by neurological changes that can include sensory deficits, drowsiness, delirium, seizures and coma, and can be fatal if not rapidly treated.

Bariatric Surgery and Diabetes

It is possible to achieve complete remission of type 2 diabetes following bariatric surgery, with recent research indicating that the majority of obese individuals with type 2 diabetes who undergo gastric bypass surgery will achieve complete remission within a year. Postsurgical diabetes outcomes are closely related to duration of diabetes and insulin use and independent of initial weight or postsurgical weight loss.

Bariatric Surgery May Help Cure Diabetes

Diabetes duration and the requirement for medication to manage the condition are both linked to decreased beta cell function and it is likely that residual beta cell function is a significant factor in determining the extent of remission attainable.

Purely restrictive procedures such as the laparoscopic band are thought to improve diabetes by facilitating weight loss, whilst procedures that involve a malabsorbtive component such as the Roux-en-Y gastric bypass (RYGB) or gastric sleeve have a more complex metabolic impact, with research indicating that improvements in type 2 diabetes can occur prior to significant weight loss following gastric bypass surgery. Normalization of blood glucose levels in as little as two weeks postoperatively has also been observed in some individuals.  In the longer term, malabsorbtive procedures typically result in greater remission of diabetes and greater weight loss.

Less data exists on the effects of bariatric surgery in relation to type 1 diabetes. The evidence that does exist appears to suggest that postsurgical weight loss can lead to improved insulin sensitivity in obese individuals with type 1 diabetes, but is typically not sufficient to achieve significantly improved glucose control.

Pregnancy outcomes for previously obese women are generally improved following bariatric surgery, and several studies have reported reduced incidence of Gestational diabetes mellitus in women who have previously undergone a bariatric procedure when compared to women with deliveries prior to bariatric surgery.