“Factors released from adipose tissue”
“Leptin — Leptin is produced by adipocytes and is secreted in proportion to adipocyte mass. It signals the hypothalamus about the quantity of stored fat. Studies in humans and animals have shown that leptin deficiency and leptin resistance are associated with obesity and insulin resistance.”
“Adiponectin — Adiponectin, an adipocyte-derived cytokine, reduces levels of blood free fatty acids and has been associated with improved lipid profiles, better glycemic control, and reduced inflammation in diabetic patients. Adiponectin has also been inversely associated with risk for diabetes in the non-diabetic population.”
“A number of observations suggest that deficiency of adiponectin, an adipocyte-derived hormone, plays a role in the development of insulin resistance and subsequent type 2 diabetes:
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“Adiponectin, and adiponectin receptors, may become an important target in the management of diabetes. Two studies have suggested that dietary cereal fiber and reduced glycemic load can increase adiponectin in diabetic men and women.”
“In addition to its strong association with type 2 diabetes risk, preliminary data suggest that adiponectin may be moderately associated with cardiovascular morbidity and mortality. High adiponectin concentrations are associated with a favorable cardiovascular risk profile. However, the relationship is more complex. High adiponectin concentrations have also been associated with increased all-cause and cardiovascular mortality. The discrepancy may be related to the patient population studied (men versus women, older versus younger, prevalent cardiovascular disease). In addition, adiponectin may not directly affect cardiovascular risk, but may be a marker of other risks. Additional studies are needed to clarify the relationship between adiponectin and cardiovascular disease.”
“Tumor necrosis factor-alpha — Studies in genetically obese animals suggest that increased release of TNF-alpha (TNFa) from adipose tissue may play a major role in the impairment in insulin action.”
Tumor necrosis factor-alpha is an inflammation thing.
“Chemokine molecules — Chemokines (chemotactic proinflammatory cytokines) are a family of low molecular weight proteins that are potent chemoattractants of leukocytes and may modulate the formation of reactive oxygen species and cytokines.” One of them is called CXCL5. “CXCL5 may be another link between obesity, inflammation, and insulin resistance.”
“DRUG-INDUCED HYPERGLYCEMIA — A large number of drugs can impair glucose tolerance; they act by decreasing insulin secretion, increasing hepatic glucose production, or causing resistance to the action of insulin. Included in this list are glucocorticoids, oral contraceptives, several classes of antihypertensive drugs such as beta blockers, thiazide diuretics, nicotinic acid, statins, protease inhibitors used for the treatment of HIV infection, gonadotropin releasing hormone agonists used for the treatment of prostate cancer, tacrolimus, sirolimus, and cyclosporine used primarily to prevent transplant rejection, and some of the atypical antipsychotic agents.”
“Thiazide diuretics — Treatment with thiazide diuretics is associated with an increase in fasting plasma glucose (FPG) and risk of developing type 2 diabetes. However, a substantial increase in FPG is unusual, even in patients with type 2 diabetes, with the currently recommended regimen of low-dose thiazide therapy (eg, 12.5 to a maximum of 25 mg of hydrochlorothiazide). Concurrent hypokalemia appears to play an important role, as evidenced by a small study showing no change in glucose tolerance if urinary losses are replaced by potassium supplements. Subsequent analyses of larger trials confirmed the association between hypokalemia and a higher probability of developing type 2 diabetes. As an example, in the Systolic Hypertension in Elderly Program trial, the risk of diabetes with use of a thiazide (chlorthalidone) was significantly attenuated when adjusted for changes in serum potassium. Each 0.5 mEq/L decrease in serum potassium was associated with a 45 percent higher risk of new diabetes. The putative mechanism for this association is a failure of potassium channels to close in response to rising plasma glucose concentrations, with a resultant decrease in insulin secretion.”
“Antipsychotics — In patients with preexisting diabetes, the initiation of atypical or typical antipsychotic agents has been associated with worsening hyperglycemia . In addition, some of the atypical antipsychotic agents, in particular, clozapine and olanzapine, have been associated with weight gain, obesity, hypertriglyceridemia, and development of diabetes mellitus. The mechanism(s) by which they cause the metabolic syndrome have not been defined. An American Diabetes Association consensus panel concluded that data on risperidone and quetiapine show an increased risk for weight gain, but conflicting data on diabetes and dyslipidemia risk. The panel also concluded that patients taking ziprasidone and aripiprazole are not at increased risk for developing diabetes or dyslipidemia.”
“The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin's A-chain to its B-chain in the proinsulin molecule.In the insulin synthesis pathway, first preproinsulin is translocated into the endoplasmic reticulum of beta cells of the pancreas with an A-chain, a C-peptide, a B-chain, and a signal sequence. The signal sequence is cleaved from the N-terminus of the peptide by a signal peptidase, leaving proinsulin. After proinsulin is packaged into vesicles in the Golgi apparatus (beta-granules), the C-peptide is removed, leaving the A-chain B-chain, bound together by disulfide bonds, that constitute the insulin molecule.”
“Clinical uses of C-peptide testing
“Plasminogen activator inhibitor — Plasminogen activator inhibitor 1, an inhibitor of fibrinolysis, is another protein related to adipocytes. It is also secreted from endothelial cells, mononuclear cells, hepatocytes, and fibroblasts and has been associated with an increased risk for cardiovascular disease. (body mass index, visceral fat, lipids, hypertension, and fasting glucose.”
“Obestatin — Obestatin, a hormone that was isolated from rat stomach, is encoded by the ghrelin gene, and opposes the effects of ghrelin on food intake. Treatment of rats with obestatin suppresses food intake, inhibits jejunal contraction, and decreases weight gain. Circulating obestatin concentrations are decreased in individuals with diabetes and impaired glucose tolerance compared with normal glucose tolerance. In addition, expression of the obestatin receptor in adipose tissue is down-regulated in obesity-associated type 2 diabetes, but not in normoglycemic obese subjects, suggesting that obestatin may play a role in glucose regulation and development of type 2 diabetes, independent of obesity.”
“Adjusted incidence of type 2 diabetes mellitus in 5990 men in relation to BMI (in kg/m2) and the level of physical activity (in kcal/week). The risk of type 2 diabetes was directly related to BMI, while regular exercise was protective except for in men with a BMI below 24” (‘cuz they are already there.)”
Stuffing your face causes obesity and obesity (and the type of foods you eat to get there) seems to cause more inflammation in the body which worsens hardening of the arteries, which kills you.
“Many studies have focused on the role of inflammation as a common mediator linking obesity to both the pathogenesis of diabetes and atherosclerosis. The incidence of type 2 diabetes has been correlated with increased levels of markers of inflammation, including C reactive protein, IL-6, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor (TNF)-alpha, and white cell count. Adipokines, factors released from adipose tissue, stimulate inflammatory activity which correlates with insulin resistance as demonstrated in mouse models (see below). Intensive lifestyle interventions have been shown to decrease markers of inflammation. Anti-inflammatory properties of medications including thiazolidinediones and statins may contribute therapeutic benefit beyond their activity to lower glucose and cholesterol levels respectively. Among patients with rheumatoid arthritis or psoriasis, use of anti-inflammatory disease-modifying antirheumatic drugs, such as TNF inhibitors and hydroxychloroquine, is associated with a lower incidence of diabetes than other agents.”
Makes sense to me.
Here’s some stuff we’ve learned that tells you fat is where it’s at, but not in a good way.
Diabetes and Obesity
This little compilation is a result of my recent reading regarding type 2 diabetes aka adult onset diabetes. The statistics and the stuff in quotes are taken from UpToDate. I put it in quotes so you know I did not write the dorky stuff. I’m showing you some of the things we know about obesity, diabetes, and inflammation so that you understand there is more to our recommendation than just that you really don’t look good in those skinny jeans.
Obesity is caused by eating too much or eating and drinking too much on a regular basis. It’s currently an epidemic in this country. Look around you. And those television ads…!!!
My concern about including this technical stuff, beside your risk of dozing off and falling off the couch, is that you’ll think we have this all figured out and will come up with a pill to solve the problem. We don’t. And we won’t. It’s up to you.
I included a couple paragraphs at the end to warn you that some of the medicines we throw at you can cause or worsen diabetes. So it’s not all hoagies and beer.
The last couple of paragraphs are on c-peptide. Endocrinologists and some primary care docs who know too much order c-peptide when evaluating diabetes. I've been reading the lab reports for years. Never knew exactly what it was or what it meant. Bet that reassures you. So there it is. Now I know and you know, and I think most of the time when they order it, they are just wasting your blood and your insurance company’s money.”
Another thing you learn from this research stuff is that being a research rat or mouse is not a good career move.
Enough hyperbole. Now comes the boring stuff.
“The prevalence of impaired glucose tolerance and type 2 diabetes has increased dramatically in the United States population in the past two decades. The most striking features in these groups and of most patients who develop type 2 diabetes are INCREASED WEIGHT GAIN and DECREASED PHYSICAL ACTIVITY, each of which increases the risk of diabetes.”
“Importance of body weight and exercise on development of type 2 diabetes is shown in this graph. It shows that the heavier you are and the less you exercise, the more likely you are to develop diabetes.”
BMI: body mass index. That’s calculated by dividing your weight by your height. BMI >25 is overweight. BMI of >30 is obese. BMI >40 is called morbid obesity. Not a good thing.