Tag Archives: insulin

If You’re Having Bariatric Surgery to Treat Your Type 2 Diabetes, You May Want RYGB Instead of LAGB

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An article at Diabetes Care suggests that insulin-treated T2 diabetics getting bariatric surgery were almost twice as likely to get off insulin if they had roux-en-Y gastric bypass rather than laparoscopic adjustable gastric banding. The former procedure is also generally more effective for weight loss.

If you think bariatric surgery is a sure-fire cure for type 2 diabetes, it’s not.

Steve Parker, M.D.

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Could Glucagon Be Just as Important as Insulin in Diabetes?

I couldn't find a pertinent picture

I couldn’t find a pertinent picture

Everybody knows that insulin is the key hormone gone haywire in diabetes, right? Did you know it’s not the only one out of whack? Roger Unger and Alan Cherrington in The Journal of Clinical Investigation point out that another hormone—glucagon—is also very important in regulation of blood sugar in both types of diabetes.

Insulin has a variety of actions the ultimately keep blood sugar levels from rising dangerously high. Glucagon, on the other hand, keeps blood sugar from dropping too low. For instance, when you stop eating food, as in an overnight or longer fast, glucagon stimulates glucose (sugar) production by your liver so you don’t go into a hypoglycemic coma and die. It does the same when you exercise, as your muscles soak up glucose from your blood stream.

Glucagon works so well to raise blood sugar that we inject it into diabetics who are hypoglycemic but comatose or otherwise unable to swallow carbohydrates.

Glucagon also has effects on fatty acid metabolism, ketone production, and liver protein metabolism, but this post is already complicated enough.

So where does glucagon come from? The islets of Langherhans, for one. You already know the healthy pancreas has beta cells that produce insulin. The pancreas has other cells—alpha or α cells—that produce glucagon. Furthermore, the stomach and duodenum (the first part of the small intestine) also have glucagon-producing alpha cells. The insulin and glucagon work together to keep blood sugar in an fairly narrow range. Insulin lowers blood sugar, glucagon raises it. It’s sort of like aiming for a hot bath by running a mix of cold and very hot water.

Update: I just licensed this from Shutterstock.com

Update: I just licensed this from Shutterstock.com

Ungar and Cherrington say that one reason it’s so hard to tightly control blood sugars in type 1 diabetes is because we don’t address the high levels of glucagon. The bath water’s not right because we’re fiddling with just one of the faucets. Maybe we’ll call this the Goldilocks Theory of Diabetes.

When you eat carbohydrates, your blood sugar starts to rise. Beta cells in the healthy pancreas start secreting insulin to keep a lid on the blood sugar rise. This is not the time you want uncontrolled release of glucagon from the alpha cells, which would work to raise blood sugars further. Within the pancreas, beta and alpha cells are in close proximity. Insulin from the beta cells directly affects the nearby alpha cells to suppress glucagon release. This localized hormone effect is referred to as “paracrine guidance” in the quote below, and it takes very little insulin to suppress glucagon.

From the Ungar and Cherrington article:

Here, we review evidence that the insulinocentric view of metabolic homeostasis is incomplete and that glucagon is indeed a key regulator of normal fuel metabolism, albeit under insulin’s paracrine guidance and control. Most importantly, we emphasize that, whenever paracrine control by insulin is lacking, as in T1DM, the resulting unbridled hyperglucagonemia is the proximal cause of the deadly consequences of uncontrolled diabetes and the glycemic volatility of even “well-controlled” patients.

*  *  *

All in all, it would seem that conventional monotherapy with insulin is incomplete because it can provide paracrine suppression of glucagon secretion only by seriously overdosing the extrapancreatic tissues.

So What?

Elucidation of diabetes’ disease mechanisms (pathophysiology) can lead to new drugs or other therapies that improve the lives of diabetics. A potential drug candidate is leptin, known to suppress glucagon hyper secretion in rodents with type 1 diabetes.

RTWT.

Steve Parker, M.D.

PS: Amylin is yet another hormone involved in blood sugar regulation, but I’ll save that for another day. If you can’t wait, read about it here in my review of pramlintide, a drug for type 1 diabetes.

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What Causes Type 2 Diabetes?

diabetic diet, low-carb Mediterranean Diet, low-carb, Conquer Diabetes and Prediabetes

Stop reading this sciencey post when you get bored

According to Roy Taylor, “type 2 diabetes is a potentially reversible metabolic state precipitated by the single cause of chronic excess intraorgan fat.” The organs accumulating fat are the liver and pancreas. He is certain “…that the disease process can be halted with restoration of normal carbohydrate and fat metabolism.” I read Taylor’s article published earlier this year in Diabetes Care.

[Do you remember that report in 2011 touting cure of T2 diabetes with a very low calorie diet? Taylor was the leader. The study involved only 11 patients, eating 600 calories a day for eight weeks.]

Dr. Taylor (M.D.) says that severe calorie restriction is similar to the effect of bariatric surgery in curing or controlling diabetes. Within a week of either intervention, liver fat content is greatly reduced, liver insulin sensitivity returns, and fasting blood sugar levels can return to normal. During the first eight weeks after intervention, pancreatic fat content falls, with associated steadily increasing rates of insulin secretion by the pancreas beta cells.

bariatric surgery, Steve Parker MD

Band Gastric Bypass Surgery (not the only type of gastric bypass): very successful at “curing” T2 diabetes if you survive the operation

Taylor’s ideas, by the way, dovetail with Roger Unger’s 2008 lipocentric theory of diabetes. Click for more ideas on the cause of T2 diabetes.

Here are some scattered points from Taylors article. He backs up most of them with references:

  • In T2 diabetes, improvement in fasting blood sugar reflects improved liver insulin sensitivity more than muscle insulin sensitivity.
  • The more fat accumulation in the liver, the less it is sensitive to insulin. If a T2 is treated with insulin, the insulin dose is positively linked to how much fat is in the liver.
  • In a T2 who starts insulin injections, liver fat stores tend to decrease. That’s because of suppression of the body’s own insulin delivery from the pancreas to the liver via the portal vein.
  • Whether obese or not, those with higher circulating insulin levels “…have markedly increased rates of hepatic de novo lipogenesis.” That means their livers are making fat. That fat (triglycerides or triacylglycerol) will be either burned in the liver for energy (oxidized), pushed into the blood stream for use elsewhere, or stored in the liver. Fatty acids are components of triglycerides. Excessive fatty acid intermediaries in liver cells—diglycerides and ceramide—are thought to interfere with insulin’s action, i.e., contribute to insulin resistance in the liver.
  • “Fasting plasma glucose concentration depends entirely on the fasting rate of hepatic [liver] glucose production and, hence, on its sensitivity to suppression by insulin.”
  • Physical activity, low-calorie diets, and thiazolidinediones reduce the pancreas’ insulin output and reduce liver fat levels.
  • Most T2 diabetics have above-average liver fat content. MRI scans are more accurate than ultrasound for finding it.
  • T2 diabetics have on average only half of the pancreas beta cell mass of non-diabetics. As the years pass, more beta cells are lost. Is the a way to preserve these insulin-producing cells, or to increase their numbers? “…it is conceivable that removal of adverse factors could result in restoration of normal beta cell number, even late in the disease.”
  • “Chronic exposure of [pancreatic] beta cells to triacylglycerol [triglycerides] or fatty acids…decreases beta cell capacity to respond to an acute increase in glucose levels.” In test tubes, fatty acids inhibit formation of new beta cells, an effect enhanced by increased glucose concentration.
  • There’s a fair amount of overlap in pancreas fat content comparing T2 diabetics and non-diabetics. It may be that people with T2 diabetes are somehow more susceptible to adverse effects of the fat via genetic and epigenetic factors.
  • “If a person has type 2 diabetes, there is more fat in the liver and pancreas than he or she an cope with.”
  • Here’s Dr. Taylor’s Twin Cycle Hypothesis of Etiology of Type 2 Diabetes: “The accumulation of fat in liver and secondarily in the pancreas will lead to self-reinforcing cycles that interact to bring about type 2 diabetes. Fatty liver leads to impaired fasting glucose metabolism and increases export of VLDL triacylglcerol [triglycerides], which increases fat delivery to all tissues, including the [pancreas] islets. The liver and pancreas cycles drive onward after diagnosis with steadily decreasing beta cell function. However, of note, observations of the reversal of type 2 diabetes confirm that if the primary influence of positive calorie balance is removed, the the processes are reversible.”
diabetic diet, etiology of type 2 diabetes, Roy Taylor, type 2 diabetes reversal

Figure 6 from the article: Dr. Taylor’s Twin Cycle Hypothesis of Etiology of Type 2 Diabetes

  • The caption with Figure 6 states: “During long-term intake of more calories than are expended each day, any excess carbohydrate must undergo de novo lipogenesis [creation of fat], which particularly promotes fat accumulation in the liver.”
  • “The extent of weight gloss required to reverse type 2 diabetes is much greater than conventionally advised.” We’re looking at around 15 kg (33 lb) or 20% of body weight, assuming the patient is obese to start.  “The initial major loss of body weight demands a substantial reduction in energy intake. After weight loss, steady weight is most effectively achieved by a combination of dietary restriction and physical activity.”

Dr. Taylor doesn’t specify how much calorie restriction he recommends, but reading between the lines, I think he likes his 600 cals/day for eight weeks program. That will have a have a high drop-out rate. I suspect a variety of existing ketogenic diets may be just as successful and more realistic, even if it takes more than eight weeks. I wonder how many of the 11 “cures” from the 2011 study have persisted.

Steve Parker, M.D.

Reference: Taylor, Roy. Type 2 diabetes: Etiology and reversibility. Diabetes Care, April 2013, vol. 36, no. 4, pp:1047-1055.

Update December 16, 2013:

Some wild and crazy guys tried this method at home. Click for results.

h/t commenter PhilT.

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Moderate-Carb Diet No Better Than Standard High-Carb Diet In Gestational Diabetes

…according to a report at MedPageToday.

Women with gestational diabetes were randomized to either a 40% carb diet or 55% carb diet. The same numbers in each group ended up needing insulin therapy to control blood sugars.

Both groups ate the same amount of protein. The lower-carb group replaces some carbs with fat.

Pregnancy outcomes were similar in both groups.

Critics wonder if stricter carbohydrate restriction would have been more effective.

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What Causes Type 2 Diabetes?

Prediabetes and type 2 diabetes are epidemics because of excessive consumption of refined sugars and starches, and lack of physical activity.  I can’t prove it; nevertheless that’s my impression after years of pondering the nutrition science literature.

I could be wrong.  I reserve the option to change my mind based on evidence as it becomes available.  That’s one of the great things about science.  Accurately identifying the cause of diabetes could provide strong clues about optimal prevention and treatment strategies.

Genetics undoubtedly plays a major role in diabetes, but the gene pool hasn’t changed much over the last several decades as type 2 diabetes rates have soared.

The problem in type 2 diabetes and prediabetes is that the body cannot handle ingested carbohydrates in the normal fashion. In a way, dietary carbohydrates (carbs) have become toxic instead of nourishing. This is a critical point, so let’s take time to understand it.

NORMAL DIGESTION AND CARBOHYDRATE HANDLING

The major components of food are fats, proteins, and carbohydrates. We digest food either to get energy, or to use individual components of food in growth, maintenance, or repair of our own body parts.

We need some sugar (also called glucose) in our bloodstream at all times to supply us with immediate energy. “Energy” refers not only to a sense of muscular strength and vitality, but also to fuel for our brain, heart, and other automatic systems. Our brains especially need a reliable supply of bloodstream glucose.

In a normal, healthy state, our blood contains very little sugar—about a teaspoon (5 ml) of glucose. (We have about one and a third gallons (5 liters) of blood circulating. A normal blood sugar of 100 mg/dl (5.56 mmol/l) equates to about a teaspoon of glucose in the bloodstream.)

Our bodies have elaborate natural mechanisms for keeping blood sugar normal. They work continuously, a combination of removing and adding sugar from the bloodstream to keep it in a healthy range (70 to 140 mg/dl, or 3.9 to 7.8 mmol/l). These homeostatic mechanisms are out of balance in people with diabetes and prediabetes.

By the way, glucose in the bloodstream is commonly referred to as “blood sugar,” even though there are many other types of sugar other than glucose. In the U.S., blood sugar is measured in units of milligrams per deciliter (mg/dl), but other places measure in millimoles per liter (mmol/l).

When blood sugar levels start to rise in response to food, the pancreas gland—its beta cells, specifically—secrete insulin into the bloodstream to keep sugar levels from rising too high. The insulin drives the excess sugar out of the blood, into our tissues. Once inside the tissues’ cells, the glucose will be used as an immediate energy source or stored for later use. Excessive sugar is stored either as body fat or as glycogen in liver and muscle.

When we digest fats, we see very little direct effect on blood sugar levels. That’s because fat contains almost no carbohydrates. In fact, when fats are eaten with high-carb foods, they tend to slow the rise and peak in blood sugar you would see if you had eaten the carbs alone.

Ingested protein can and does raise blood sugar, usually to a mild degree. As proteins are digested, our bodies can make sugar (glucose) out of the breakdown products. The healthy pancreas releases some insulin to keep the blood sugar from going too high.

In contrast to fats and proteins, carbohydrates in food cause significant—often dramatic—rises in blood sugar. Our pancreas, in turn, secretes higher amounts of insulin to prevent excessive elevation of blood glucose. Carbohydrates are easily digested and converted into blood sugar. The exception is fiber, which is indigestible and passes through us unchanged.

During the course of a day, the pancreas of a healthy adult produces an average of 40 to 60 units of insulin. Half of that insulin is secreted in response to meals, the other half is steady state or “basal” insulin. The exact amount of insulin depends quite heavily on the amount and timing of carbohydrates eaten. Dietary protein has much less influence. A pancreas in a healthy person eating a very-low-carb diet will release substantially less than 50 units of insulin a day.

To summarize thus far: dietary carbs are the major source of blood sugar for most people eating “normally.” Carbs are, in turn, the main cause for insulin release by the pancreas, to keep blood sugar levels in a safe, healthy range.

Hang on, because we’re almost done with the basic science!

You deserve a break

CARBOHYDRATE  HANDLING  IN  DIABETES  &  PREDIABETES

Type 2 diabetics and prediabetics absorb carbohydrates and break them down into glucose just fine. Problem is, they can’t clear the glucose out of the bloodstream normally. So blood sugar levels are often in the elevated, poisonous range, leading to many of the complications of diabetes.

Remember that insulin’s primary function is to drive blood glucose out of the bloodstream, into our tissues, for use as immediate energy or stored energy (as fat or glycogen).

In diabetes and prediabetes, this function of insulin is impaired.

The tissues have lost some of their sensitivity to insulin’s action. This critical concept is called insulin resistance. Insulin still has some effect on the tissues, but not as much as it should. Different diabetics have different degrees of insulin resistance, and you can’t tell by just looking.  (There are several other hormones involved in regulation of blood sugar.)

Did you know that people who work at garbage dumps, sewage treatment plants, and cattle feedlots get used to the noxious fumes after a while? They aren’t bothered by them as much as they were at first. Their noses are less sensitive to the fumes. You could call it fume resistance. In the same fashion, cells exposed to high insulin levels over time become resistant to insulin.

Insulin resistance occurs in most cases of type 2 diabetes and prediabetes. So what causes the insulin resistance? It’s debatable. In many cases it’s related to overweight, physical inactivity, and genetics. A high-carbohydrate diet may contribute. A few cases are caused by drugs. Some cases are a mystery.

To overcome the body tissue’s resistance to insulin’s effect, the pancreas beta cells pump even more insulin into the bloodstream, a condition called hyperinsulinemia. Some scientists believe high insulin levels alone cause some of the damage associated with diabetes. Whereas a healthy person without diabetes needs about 50 units of insulin a day, an obese non-diabetic needs about twice that to keep blood sugars in check. Eventually, in those who develop diabetes or prediabetes, the pancreas can’t keep up with the demand for more insulin to overcome insulin resistance. The pancreas beta cells get exhausted and start to “burn out.” That’s when blood sugars start to rise and diabetes and prediabetes are easily diagnosed. So, insulin resistance and high insulin production have been going on for years before diagnosis. By the time of diagnosis, 50% of beta cell function is lost.

Steve Parker, M.D.

EXTRA  CREDIT  FOR  INQUISITIVE  MINDS

You’ve learned that insulin’s main action is to lower blood sugar by transporting it into the cells of various tissues. But that’s not all insulin does. It also 1) impairs breakdown of glycogen into glucose, 2) stimulates glycogen formation, 3) inhibits formation of new glucose molecules by the body, 4) promotes storage of triglycerides in fat cells (i.e., lipogenesis, fat accumulation), 5) promotes formation of fatty acids (triglyceride building blocks) by the liver, 6) inhibits breakdown of stored triglycerides, and 7) supports body protein production.

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How To Recognize and Treat Hypoglycemia (Low Blood Sugar)

Insulin and sulfonylurea drugs are common causes of hypoglycemia

Insulin and sulfonylurea drugs are common causes of hypoglycemia

Hypoglycemia is the biggest immediate risk for a diabetic on drugs starting a carbohydrate-restricted diet such as the Low-Carb Mediterranean Diet. Traditional calorie-restricted diets also have the potential to cause hypoglycemia.

SYMPTOMS

Your personal physician and other healthcare team members should teach you how to recognize and manage hypoglycemia.  Hypoglycemial means an abnormally low blood sugar (under 60–70 mg/dl or 3.33–3.89 mmol/l) associated with symptoms such as weakness, malaise, anxiety, irritability, shaking, sweating, hunger, fast heart rate, blurry vision, difficulty concentrating, or dizziness. Symptoms often start suddenly and without obvious explanation. If not recognized and treated, hypoglycemia can lead to incoordination, altered mental status (fuzzy thinking, disorientation, confusion, odd behavior, lethargy), loss of consciousness, seizures, and even death (rare).

You can imagine the consequences if you develop fuzzy thinking or lose consciousness while driving a car, operating dangerous machinery, or scuba diving.

TREATMENT

Immediate early stage treatment involves ingestion of glucose as the preferred treatment—15 to 20 grams. You can get glucose tablets or paste at your local pharmacy without a prescription. Other carbohydrates will also work: six fl oz (180 ml) sweetened fruit juice, 12 fl oz (360 ml) milk, four tsp (20 ml) table sugar mixed in water, four fl oz (120 ml) soda pop, candy, etc. Fifteen to 30 grams of glucose or other carbohydrate should do the trick. Hypoglycemic symptoms respond within 20 minutes.

If level of consciousness is diminished such that the person cannot safely swallow, he will need a glucagon injection. Non-medical people can be trained to give the injection under the skin or into a muscle. Ask your doctor if you are at risk for severe hypoglycemia. If so, ask him for a prescription so you can get an emergency glucagon kit from a pharmacy.

Some people with diabetes, particularly after having the condition for many years, lose the ability to detect hypoglycemia just by the way they feel. This “hypoglycemia unawareness” is obviously more dangerous than being able to detect and treat hypoglycemia early on. Blood sugar levels may continue to fall and reach a life-threatening degree. Hypoglycemia unawareness can be caused by impairment of the nervous system (autonomic neuropathy) or by beta blocker drugs prescribed for high blood pressure or heart disease. People with hypoglycemia unawareness need to check blood sugars more frequently, particularly if driving a car or operating dangerous machinery.

Do not assume your sugar is low every time you feel a little hungry, weak, or anxious. Use your home glucose monitor for confirmation when able.

If you do experience hypoglycemia, discuss management options with your doctor: downward medication adjustment, shifting meal quantities or times, adjustment of exercise routine, eating more carbohydrates, etc. If you’re trying to lose weight or control high blood sugars, reducing certain diabetic drugs makes more sense than eating more carbs. Eating at regular intervals three or four times daily may help prevent hypoglycemia. Spreading carbohydrate consumption evenly throughout the day may help. Someone most active during daylight hours as opposed to nighttime will generally do better eating carbs at breakfast and lunch rather than concentrating them at bedtime.

DRUG  ADJUSTMENTS  TO  AVOID  HYPOGLYCEMIA

Diabetics considering or following a low-carb or very-low-carb ketogenic diet must work closely with their personal physician and dietitian, especially to avoid hypoglycemia caused by certain classes of diabetic drugs. Two common diabetes drug classes that cause hypoglycemia are the insulins and sulfonylureas. More are listed below. Those who don’t know the class of their diabetic medication should ask their physician or pharmacist.

Clinical experience with thousands of patients has led to generally accepted guidelines that help avoid hypoglycemia in diabetics on medications.

Diabetics and prediabetics not being treated with pills or insulin rarely need to worry about hypoglycemia.

Similarly, diabetics treated only with diet, metformin, colesevalam, and/or an alpha-glucosidase inhibitor (acarbose, miglitol) should not have much, if any, trouble with hypoglycemia. The DPP4-inhibitors (sitagliptan and saxagliptin) do not seem to cause low glucose levels, whether used alone or combined with metformin or a thiazoladinedione.

Thiazolidinediones by themselves cause hypoglycemia in only 1 to 3% of users, but might cause a higher percentage in people on a reduced calorie diet. Bromocriptine may slightly increase the risk of hypoglycemia.

THESE DRUGS MAY CAUSE HYPOGLYCEMIA

Type 2 diabetics are at risk for hypoglycemia if they use the following drug classes. Also listed are a few of the individual drugs in some classes:

■  insulin

■  sulfonylureas: glipizide, glyburide, glimiperide, chlorpropamide, acetohexamide, tolbutamide

■  meglitinides: repaglinide, nateglinide

■  pramlintide plus insulin

■  exenatide plus sulfonylurea

■  possibly thiazolidinediones: pioglitazone, rosiglitazone

■  possibly bromocriptine

Open wide!

Open wide!

Remember, drugs have both generic and brand names. The names vary from country to country, as well as by manufacturer. If you have any doubt about whether your diabetic drug has the potential to cause hypoglycemia, ask your physician or pharmacist.

MANAGEMENT STRATEGIES TO AVOID HYPOGLYCEMIA

Common management strategies for diabetics on the preceding drugs and starting a very-low-carb diet include:

■  reduce the insulin dose by half

■  change short-acting insulin to long-acting (such as glargine)

■  stop the sulfonylurea, or reduce dose by half

■  reduce the thiazolidinedione by half

■  stop the meglitinide, or reduce the dose by half

■  monitor blood sugars frequently, such as four times daily, at least until a stable pattern is established

■  spread what few carbohydrates are eaten evenly throughout the day

Management also includes frequent monitoring of glucose levels with a home glucose monitor, often four to six times daily. Common measurement times are before meals and at bedtime. It may be helpful to occasionally wake at 3 AM and check a sugar level. To see the effect of a particular food or meal on glucose level, check it one or two hours after eating. Keep a record. When eating patterns are stable, and blood sugar levels are reasonable and stable, monitoring can be done less often. When food consumption or exercise habits change significantly, check sugar levels more often.

If you’re thinking that many type 2 diabetics on low-carb and very-low-carb ketogenic diets use fewer diabetic medications, you’re right. That’s probably a good thing since the long-term side effects of many of the drugs we use are unknown. Remember Rezulin (troglitazone)? Introduced in 1997, it was pulled off the U.S. market in 2001 because of fatal liver toxicity. More recently, rosiglitazone usage has been highly restricted due to concern for heart toxicity.

Steve Parker, M.D.

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What Causes Type 2 Diabetes?

“Beats me. I teach math!”

I have no simple answer for you, unfortunately.

You can lower your risk of type 2 diabetes significantly by avoiding overweight and obesity, by exercising regularly, and by choosing the right parents.  These provide clues as to the causes of diabetes.  The Mediterranean diet also prevents diabetes.

UpToDate.com offers a deceptively simple answer:

Type 2 diabetes mellitus is caused by a combination of varying degrees of insulin resistance and relative insulin deficiency. [Insulin is the pancreas hormone that lowers blood sugar.] Its occurrence most likely represents a complex interaction among many genes and environmental factors, which are different among different populations and individuals.

So, what causes the insulin resistance and relative insulin deficiency?

Understanding the pathogenesis [cause] of type 2 diabetes is complicated by several factors. Patients present with a combination of varying degrees of insulin resistance and relative insulin deficiency, and it is likely that both contribute to type 2 diabetes. Furthermore, each of the clinical features can arise through genetic or environmental influences, making it difficult to determine the exact cause in an individual patient. Moreover, hyperglycemia itself can impair pancreatic beta cell function and exacerbate insulin resistance, leading to a vicious cycle of hyperglycemia causing a worsening metabolic state.

The UpToDate article then drones on for a several thousand words discussing mouse studies, various genes, free fatty acids, adiponectin, leptin, amylin, insulin secretion, insulin resistance, impaired insulin processing, insulin action, body fat distribution, inflammation, various inflammatory markers, low birth weight, high birth rate, prematurity, etc.  More excerpts:

Increased free fatty acid levels, inflammatory cytokines from fat, and oxidative factors, have all been implicated in the pathogenesis of metabolic syndrome, type 2 diabetes, and their cardiovascular complications.

Insulin resistance may, at least in part, be related to substances secreted by adipocytes [fat cells] (“adipokines” including leptin adiponectin, tumor necrosis factor alpha, and resistin).

Type 2 diabetes most likely represents a complex interaction among many genes and environmental factors.

That’s the simplest answer I can give now.

Steve Parker, M.D.

Reference: “The Pathogensis of Type 2 Diabetes Mellitus”  by David K McCulloch, MD, and R Paul Robertson, MD, at UpToDate.com, updated June 2012, and accessed November 19, 2012.

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