Summary of Study Results
linking Diabetes with PCBs and Dioxin
The 66 studies summarized below showed insulin effects, changes in glucose metabolism, insulin resistance, pancreatic damage or other possible signs of diabetes, or diabetes complications, linked to PCB and dioxin exposure. Diabetes insulin links are strong. Diabetes prevention or management may include avoidance of PCBs and dioxins in the diabetic diet. Keep in mind that not all studies are equal in size, dose or quality. Some examine the effects of old PCB commercial mixtures (which had variable composition), or just one or two individual types of PCBs (out of 209 possible.) This accounts for some of the varying results. It’s clear that not all PCBs have the same effects. The types of PCBs and dioxins which have lingered in our area and accumulated in Fox River and Green Bay fish are likely to be the more toxic and persistent PCB types.
(Each entry below represents one finding in a study
--- unless otherwise noted. Some studies had multiple findings.
For more details go to 66
Studies involving PCBs, Dioxins and Diabetes)
- the possibility exists that PCBs and diabetes are causality related
- PCB pharmacokinetics could be altered among patients with diabetes
- serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment
- diabetic rats were more vulnerable to PCB induced metabolic changes (2 studies)
- PCBs increased the rate of ascorbic acid (Vitamin C) excretion in diabetic rats 15-30 times
- PCBs increased the rate of cytochrome P-450 and b(5) elevation
- PCBs increased cholesterol in diabetic rats
- acetoacetate and beta-hydroxybutyrate in blood were markedly reduced
- decreased activity of pyruvate carboxylase, PEPck and glucose-6-phosphatase (G6Pase) in diabetic liver
- PCBs cause massive liver accumulation of uroporphyrin, which is also seen in diabetes
- PCBs induce cytochrome P450, particularly the 1A2 isozyme, which may be a factor in uroporphyrin accumulation
- ascorbic acid (Vitamin C) may counteract the effect
- chemicals which alter endocrine function (such as PCBs) may alter glucose metabolism
- Diabetes mellitus might arise as a result of occupational exposure or heighten the susceptibility to occupational diseases
- PCBs produce a release of insulin from RINm5F hormone producing cells
- non-coplanar PCBs caused the effect, but coplanar PCBs did not
- PCBs induce a release of insulin
- insulin release is linked to PCB induced increase in intracellular free calcium
- calcium and CaM kinase II may play a role in PCB-induced insulin release
- insulin release by PCBs is independent of the activation of MAPKs
- insulin sensitivity was depressed increasingly with period of administration of PCBs
- disturbed glucose and lipid metabolism
- increases in total cholesterol, HDL-C, triglyceride, lipid peroxide and T3 in blood plasma
- non-coplanar PCBs may affect insulin release
- use of Ah-receptor binding and its effects to assess PCB toxicity may no longer be defensible because of effects of non-coplanar congeners
- PCBs induce or inhibit important enzymes affecting glucose and lipid metabolism
- dioxin reduces glucose transport, which is an important factor in the down regulation of lipoprotein lipase (LPL) activity (certain PCBs are dioxin-like)
- depression of LPL activity in fat tissue is associated with dioxin-induced wasting syndrome and may have a role in the associated serum hyperlipidemia produced by dioxin
- PCBs and dioxin both reduce LPL activity through binding to the Ah receptor
- PCBs increased in the blood serum with the loss of body fat during the first 12-18 months, then decreased
- dioxin alters enzyme activity related to glucose metabolism (certain PCBs are dioxin-like)
- the pancreas is a target of PCB toxicity
- increased activity of the beta-cells of the pancreas (the beta-cells make insulin)
- marked dilatation of rough endoplasmic reticulum (RER) and vesiculation of RER in the beta-cells
- hyperplastic Golgi complexes in the beta-cells
- reduced number of secretory granules in the beta-cells
- increased number of mitochondria and mitochondrial changes in the beta-cells
- increased activity of the adrenal zona fasciculata
- PCBs impair enzyme regulation
- PCBs exert impacts by influencing membrane fluidity
- PCBs are selectively incorporated into the hepatopancreas in molluscs and into rat livers
- PCBs alter enzyme activity in rats
- PCB-induced effects were significantly less pronounced in old than in young animals
- while activity was induced in insuline- and triiodothyronine-containing medium, this increase was significantly greater with PCBs present.
- PCBs alter enzyme activity in the hepatopancreas of crayfish
- PCBs induce growth of pancreatic tissue inside the liver
- PCBs increase enzyme activity in the pancreas
- PCBs may be linked to an increase in fibrous areas in the pancreas of Fox River and Green Bay fish
- PCBs are Type II inducers of enzymes in the hepatopancreas of crabs
- PCBs caused severe vacuolation in the pancreatic exocrine tissue surrounding the portal veins in pinfish
- PCBs caused pancreatic duct hyperplasia, in a dose/response relationship
- both dechlorinated and regular PCBs stimulate insulin secretion
- partly degrading PCBs doesn’t change the insulin effect
- with saturating levels of insulin, enzyme activities were induced, but addition of PCBs result in an additive effect.
- PCBs influence gluconeogenic and lipogenic enzymes, in a dose-dependent manner
- some genetic strains are more sensitive to PCBs
- subchronic exposure to PCBs seems to have no effect on the plasma leptin levels or the glucose-6-phophatase activities
- significant decrease of the chaperone proteins (glucose regulated proteins) in the endoplasmic reticulum
- PCBs activate the hypothalamus-pituitary-interrenal (HPI) axis
- lower hyperglycemic response to confinement
- fat levels in the diet influence the enzyme impacts of PCB exposure
- low PCB exposures (.1 ppm) decreased serum glucose
- decreased plasma glucose levels
- enzyme activity was increased by PCBs in certain strains of mice and rats
- enzyme activity was decreased by PCBs in guinea pigs
- enzyme induction involves the Ah receptor
- PCBs may shift rats toward urea formation rather than glucose synthesis and nitrogen retention
- loss of nitrogen by the ARO group was attributed to increased excretion of urinary nitrogen, most likely as urea, in relation to the nitrogen intake
- lipids influence the action of PCBs
- PCBs, which induce hepatic P-450, had no effect on salicylate-induced nephrotoxicity nor on the covalent binding of [14C]salicylate equivalents to renal mitochondria
- PCBs increased inner membrane permeability and fragility of hepatic mitochondria
- PCBs are correlated with hypoglycemia and suppressed glucogenesis
- PCB exposure poises hepatic mitochondria toward the synthesis of urea intermediates
- study used PCB commercial mixture Aroclor 1254
- PCBs cause liver glycogen islets to disappear and dramatic local alterations of mitochondrial cristae
- dioxin is associated with an increased prevalence of diabetes and hyperinsulinemia in non-diabetic subjects (certain PCBs are dioxin-like)
- high blood dioxin levels may cause insulin resistance
- dioxin is associated with increased diabetes incidence, at background levels of dioxin exposure
- diabetes was found in six of 10 (60%) workers with current serum dioxin concentrations > 1500 pg/g lipid
- dioxin significantly increased adjusted mean serum glucose concentration
- dioxin may affect glucose metabolism
- diabetes (any mention on the death certificate) showed a negative dioxin exposure-response trend
- dioxin and insulin regulation have a compensatory metabolic relationship
- dioxin is associated with significant increases in diabetes in women
- dioxin may be associated with diabetes
- an excess of diabetes cases were associated with dioxin exposure
- dioxin increased glucose abnormalities, diabetes prevalence and use of diabetes medications
- dioxin decreased time-to-diabetes-onset
- dioxin increased serum insulin abnormalities
- dioxin has an adverse relation to diabetes mellitus, glucose metabolism, and insulin production
- dioxin exposure symptoms can be confused with diabetes symptoms [or dioxins cause diabetes?]
- diabetics may be predisposed to more toxic effects (peripheral neuropathy) as a result of dioxin exposure
- dioxin is associated with disorders of the metabolism of porphyrins, fats, carbohydrates, plasmaproteins
- most, if not all, toxic effects of dioxin are mediated more or less through the binding affinity to the Ah receptor (certain PCBs also bind to the Ah receptor)
- total fat (lipid) body content influences sensitivity or resistance to dioxin
- chronic dietary PCB exposure significantly lowers intestinal levels of stored cholecystokinin (CCK) peptide
- dioxin is associated with changed insulin levels
- significant decrease in fasting blood glucose and basal insulin level.
- dioxin-induced wasting syndrome might relate to disturbed glucose metabolism of the main organ through insufficiency of caloric intake, thyroxine (T4) and insulin
- dioxin may stimulate or mimic insulin, and influence cell growth
- dioxin reduces insulin
- dioxin reduces hepatic gluconeogenesis
- dioxin reduces the activity of PEPCK, the rate limiting enzyme of gluconeogenesis, most likely through decreased expression of the PEPCK gene
- dioxin derails glucose metabolism
- dioxin causes hypoinsulinemia
- higher overall protein phosphorylation activities
- dioxin causes a rise in protein-tyrosine kinases in pancreas at early stages of poisoning
- dioxin causes hyperlipidemia, body weight loss (particularly body fat loss), anorexia, changes in carbohydrate metabolism, and lipid peroxidation
- biochemical changes occur at very low doses, and some effects can last for long time periods
- biochemical systems particularly affected are lipoprotein lipases, low-density-lipoprotein receptors, glucose transporter proteins (GLUTs), vitamin C uptake, and insulin secretion
- dioxin causes hypophagia and body weight loss
- dioxin seems to affect the same regulation chain that is involved in the lesioning of the ventromedial hypothalamus
- dioxin causes a time- and dose-dependent decrease in cellular glucose uptake
- glucose transporters and enzymes are altered by dioxin
- dioxin inhibited breast cancer cell growth stimulated by insulin, through binding to the Ah receptor
- dioxin reduced estradiol in human luteinized granulosa cells through blockage of the mitotic signal directly or indirectly through the interaction of PTK/MAP2K and PKA signaling.
- dioxin and insulin sometimes have synergistic effects on enzyme levels
- dioxin activated insulin-like growth factor (IGF-I) signaling pathways under insulin-deficient conditions
- dioxin (and dioxin-like PCBs) may alter cell growth in human mammary epithelial cells via mimicry of growth factor receptor signaling pathways
- PCBs are known to cause acute and chronic hyperlipidemia accompanied with the loss of body fat
- the most predominant toxic expression of dioxin is hypertriglyceridemia (some PCBs are dioxin-like)
- lipid metabolism is known to play a vital role in nutritional homeostasis
- dioxin and dioxin-like PCBs affect insulin
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